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1
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Xu Q, Shao D. Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers. Front Immunol 2024; 15:1487610. [PMID: 39691707 PMCID: PMC11649667 DOI: 10.3389/fimmu.2024.1487610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 11/20/2024] [Indexed: 12/19/2024] Open
Abstract
The response rates to immunotherapy vary widely depending on the type of cancer and the specific treatment used and can be disappointingly low for many solid tumors. Fortunately, due to their complementary mechanisms of action, immunotherapy and anti-angiogenic therapy have synergistic effects in cancer treatment. By normalizing the tumor vasculature, anti-angiogenic therapy can improve blood flow and oxygenation to facilitate better immune cell infiltration into the tumor and enhance the effectiveness of immunotherapy. It also reduces immunosuppressive factors and enhances immune activation, to create a more favorable environment for immune cells to attack the tumor. Their combination leverages the strengths of both therapies to enhance anti-tumor effects and improve patient outcomes. This review discusses the vasculature-immunity crosstalk in the tumor microenvironment and summarizes the latest advances in combining anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system tumors.
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Affiliation(s)
| | - Dong Shao
- Department of Gastroenterology, The Third Affiliated Hospital of Soochow
University, Changzhou, Jiangsu, China
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2
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Wu R, Yuan S, Wang Y, Nan Y, Chen Z, Yuan H, Wang Z, Li Z, Zong D. Efficacy and safety of ramucirumab in gastric or gastroesophageal cancer: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2024; 48:102466. [PMID: 39299442 DOI: 10.1016/j.clinre.2024.102466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 08/09/2024] [Accepted: 09/17/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Ramucirumab is considered a potential treatment for gastric or gastroesophageal cancer; however, its safety has not been evaluated. This meta-analysis aimed to evaluate the efficacy and safety of ramucirumab for treating gastric or gastroesophageal cancer. METHODS The databases of PubMed, Embase, and Cochrane Library were searched through October 2023. The search focused on randomized controlled trials (RCTs) comparing ramucirumab (with or without chemotherapy) to a placebo (with or without chemotherapy) in patients with gastric or gastroesophageal cancer. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were pooled. RESULTS Seven RCTs with a total of 2613 patients were included. Compared with placebo (with or without chemotherapy), ramucirumab (with or without chemotherapy) significantly improved OS (HR: 0.90, 95% CI: 0.82-0.99, p = 0.030), PFS (HR: 0.74, 95% CI: 0.60-0.90, p = 0.003), ORR (OR: 1.39, 95% CI: 1.15-1.67, p < 0.001), and DCR (OR: 1.91, 95% CI: 1.38-2.63, p < 0.001). However, ramucirumab (with or without chemotherapy) also increased the incidence of decreased appetite (OR: 1.29, 95% CI: 1.09-1.53, p = 0.004), diarrhea (OR: 1.39, 95% CI: 1.01-1.91, p = 0.05), hypertension (OR: 3.13, 95% CI: 2.03-4.83, p < 0.00001), and bleeding or hemorrhage (OR: 2.34, 95% CI: 1.93-2.85, p < 0.00001). CONCLUSIONS Ramucirumab (with or without chemotherapy) can improve OS, PFS, ORR and DCR in patients with gastric or gastroesophageal cancer. However, it may also increase the incidence of specific AEs.
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Affiliation(s)
- Rui Wu
- School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Sijia Yuan
- Shenyang Women's and Children's Hospital, Shenyang, PR China
| | - Yuxuan Wang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Yangli Nan
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Zixiao Chen
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Hong Yuan
- School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Zixuan Wang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Zuojing Li
- School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Dongsheng Zong
- School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, PR China.
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3
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de Melo Silva AJ, de Melo Gama JE, de Oliveira SA. The Role of Bcl-2 Family Proteins and Sorafenib Resistance in Hepatocellular Carcinoma. Int J Cell Biol 2024; 2024:4972523. [PMID: 39188653 PMCID: PMC11347034 DOI: 10.1155/2024/4972523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 07/10/2024] [Accepted: 08/02/2024] [Indexed: 08/28/2024] Open
Abstract
Liver cancer has been reported to be one of the most malignant diseases in the world. It is late diagnosis consequently leads to a difficult treatment, as the cancer reached an advanced stage. Hepatocellular carcinoma (HCC) is the primary type of cancer diagnosed in the liver, with deadly characteristics and a poor prognosis. The first-in-line treatment for advanced HCC is sorafenib. Sorafenib acts by inhibiting cell proliferation and by inducing apoptosis as well as blocks receptors associated with these mechanisms. Due to its constant use, sorafenib resistance has been described, especially to proteins of the Bcl-2 family, and their overexpression of Bcl-XL and Mcl-1. This review focuses on the role of the Bcl-2 proteins in relation to sorafenib resistance as a consequence of first-in-line treatment in HCC.
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4
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Kirti A, Simnani FZ, Jena S, Lenka SS, Kalalpitiya C, Naser SS, Singh D, Choudhury A, Sahu RN, Yadav A, Sinha A, Nandi A, Panda PK, Kaushik NK, Suar M, Verma SK. Nanoparticle-mediated metronomic chemotherapy in cancer: A paradigm of precision and persistence. Cancer Lett 2024; 594:216990. [PMID: 38801886 DOI: 10.1016/j.canlet.2024.216990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 03/05/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024]
Abstract
Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.
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Affiliation(s)
- Apoorv Kirti
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | | | - Snehasmita Jena
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | - Sudakshya S Lenka
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | | | | | - Dibyangshee Singh
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | - Anmol Choudhury
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | - Rudra Narayan Sahu
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | - Anu Yadav
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | - Adrija Sinha
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
| | - Aditya Nandi
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India; Instituto de Investigaciones en Materiales, UNAM, 04510, CDMX, Mexico
| | - Pritam Kumar Panda
- Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20, Uppsala, Sweden
| | - Nagendra Kumar Kaushik
- Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 01897, Republic of Korea.
| | - Mrutyunjay Suar
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India.
| | - Suresh K Verma
- KIIT School of Biotechnology, KIIT University, Bhubaneswar, 751024, India.
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5
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Jiang S, Zhu G, Tan Y, Zhou T, Zheng S, Wang F, Lei W, Liu X, Du J, Tian M. Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis. Aging (Albany NY) 2024; 16:10321-10347. [PMID: 38874512 PMCID: PMC11236318 DOI: 10.18632/aging.205931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 04/08/2024] [Indexed: 06/15/2024]
Abstract
Microangiogenesis is an important prognostic factor in various cancers, including hepatocellular carcinoma (HCC). The Vascular Endothelial Growth Factor (VEGF) has been shown to contribute to tumor angiogenesis. Recently, several studies have investigated the regulation of VEGF production by a single gene, with few researchers exploring all genes that affect VEGF production. In this study, we comprehensively analyzed all genes affecting VEGF production in HCC and developed a risk model and gene-based risk score based on VEGF production. Moreover, the model's predictive capacity on prognosis of HCCs was verified using training and validation datasets. The developed model showed good prediction of the overall survival rate. Patients with a higher risk score experienced poor outcomes compared to those with a lower risk score. Furthermore, we identified the immunological causes of the poor prognosis of patients with high-risk scores comparing with those with low-risk scores.
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Affiliation(s)
- Shengpan Jiang
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Guoting Zhu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Yiqing Tan
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Tao Zhou
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Shilin Zheng
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Fuhua Wang
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Wenfeng Lei
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Xuan Liu
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China
| | - Jinjun Du
- Department of Hepatology and Gastroenterology, Wuhan Hospital of Traditional Chinese Medicine (The Third Clinical College of Hubei University of Chinese Medicine), Wuhan, Hubei Province, China
| | - Manman Tian
- Department of Hepatology and Gastroenterology, Wuhan Hospital of Traditional Chinese Medicine (The Third Clinical College of Hubei University of Chinese Medicine), Wuhan, Hubei Province, China
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6
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Yin X, Rong J, Shao M, Zhang S, Yin L, He Z, Wang X. Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma. J Nanobiotechnology 2024; 22:243. [PMID: 38735927 PMCID: PMC11089756 DOI: 10.1186/s12951-024-02486-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 04/17/2024] [Indexed: 05/14/2024] Open
Abstract
Hepatocellular carcinoma (HCC) represents one of the deadliest cancers globally, making the search for more effective diagnostic and therapeutic approaches particularly crucial. Aptamer-functionalized nanomaterials (AFNs), an innovative nanotechnology, have paved new pathways for the targeted diagnosis and treatment of HCC. Initially, we outline the epidemiological background of HCC and the current therapeutic challenges. Subsequently, we explore in detail how AFNs enhance diagnostic and therapeutic efficiency and reduce side effects through the specific targeting of HCC cells and the optimization of drug delivery. Furthermore, we address the challenges faced by AFNs in clinical applications and future research directions, with a particular focus on enhancing their biocompatibility and assessing long-term effects. In summary, AFNs represent an avant-garde therapeutic approach, opening new avenues and possibilities for the diagnosis and treatment of HCC.
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Affiliation(s)
- Xiujuan Yin
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Jing Rong
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Min Shao
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Saisai Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Likang Yin
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Zhenqiang He
- Clinical Medical College, Hebei University, Baoding, 071002, Hebei, China
| | - Xiao Wang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
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7
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Khafaga AF, Gaballa MMS, Karam R, Shoulah SA, Shamma RN, Khalifa NE, Farrag NE, Noreldin AE. Synergistic therapeutic strategies and engineered nanoparticles for anti-vascular endothelial growth factor therapy in cancer. Life Sci 2024; 341:122499. [PMID: 38342375 DOI: 10.1016/j.lfs.2024.122499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 01/29/2024] [Accepted: 02/07/2024] [Indexed: 02/13/2024]
Abstract
Angiogenesis is one of the defining characteristics of cancer. Vascular endothelial growth factor (VEGF) is crucial for the development of angiogenesis. A growing interest in cancer therapy is being caused by the widespread use of antiangiogenic drugs in treating several types of human cancer. However, this therapeutic approach can worsen resistance, invasion, and overall survival. As we proceed, refining combination strategies and addressing the constraint of targeted treatments are paramount. Therefore, major challenges in using novel combinations of antiangiogenic agents with cytotoxic treatments are currently focused on illustrating the potential of synergistic therapeutic strategies, alongside advancements in nanomedicine and gene therapy, present opportunities for more precise interference with angiogenesis pathways and tumor environments. Nanoparticles have the potential to regulate several crucial activities and improve several drug limitations such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance based on their unique features. The goal of this updated review is to illustrate the enormous potential of novel synergistic therapeutic strategies and the targeted nanoparticles as an alternate strategy for t treating a variety of tumors employing antiangiogenic therapy.
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Affiliation(s)
- Asmaa F Khafaga
- Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina 22758, Egypt.
| | - Mohamed M S Gaballa
- Department of Pathology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt.
| | - Reham Karam
- Department of Virology, Faculty of Veterinary Medicine, Mansoura University, 35511, Egypt.
| | - Salma A Shoulah
- Department of Animal Medicine (Infectious Diseases), Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt.
| | - Rehab N Shamma
- Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
| | - Norhan E Khalifa
- Department of Physiology, Faculty of Veterinary Medicine, Matrouh University, Matrouh 51511, Egypt.
| | - Nehal E Farrag
- Faculty of Veterinary Medicine, Alexandria University, Edfina 22758, Egypt.
| | - Ahmed E Noreldin
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.
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8
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Wang Y, Sun Y, Li X, Yu X, Zhang K, Liu J, Tian Q, Zhang H, Du X, Wang S. Progress in the treatment of malignant ascites. Crit Rev Oncol Hematol 2024; 194:104237. [PMID: 38128628 DOI: 10.1016/j.critrevonc.2023.104237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 11/14/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023] Open
Abstract
Malignant ascites occurs as a symptom of the terminal stage of cancer, affecting the quality of life through abdominal distension, pain, nausea, anorexia, dyspnea and other symptoms. We describe the current main drug treatments in addition to surgery according to the traditional and new strategies. Traditional treatments were based on anti-tumor chemotherapy and traditional Chinese medicine treatments, as well as diuretics to relieve the patient's symptoms. New treatments mainly involve photothermal therapy, intestinal therapy and targeted immunity. This study emphasizes that both traditional and new therapies have certain advantages and disadvantages, and medication should be adjusted according to different periods of use and different patients. In conclusion, this article reviews the literature to systematically describe the primary treatment modalities for malignant ascites.
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Affiliation(s)
- Yiqiu Wang
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Yunting Sun
- Hangzhou TCM Hospital Afflitiated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311121, China.
| | - Xinyue Li
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Xiaoli Yu
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Keying Zhang
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Jinglei Liu
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Qingchang Tian
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Honghua Zhang
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Xiao Du
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
| | - Shuling Wang
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, Zhejiang 311121, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
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9
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Wang L, Liu WQ, Broussy S, Han B, Fang H. Recent advances of anti-angiogenic inhibitors targeting VEGF/VEGFR axis. Front Pharmacol 2024; 14:1307860. [PMID: 38239196 PMCID: PMC10794590 DOI: 10.3389/fphar.2023.1307860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 12/11/2023] [Indexed: 01/22/2024] Open
Abstract
Vascular endothelial growth factors (VEGF), Vascular endothelial growth factor receptors (VEGFR) and their downstream signaling pathways are promising targets in anti-angiogenic therapy. They constitute a crucial system to regulate physiological and pathological angiogenesis. In the last 20 years, many anti-angiogenic drugs have been developed based on VEGF/VEGFR system to treat diverse cancers and retinopathies, and new drugs with improved properties continue to emerge at a fast rate. They consist of different molecular structures and characteristics, which enable them to inhibit the interaction of VEGF/VEGFR, to inhibit the activity of VEGFR tyrosine kinase (TK), or to inhibit VEGFR downstream signaling. In this paper, we reviewed the development of marketed anti-angiogenic drugs involved in the VEGF/VEGFR axis, as well as some important drug candidates in clinical trials. We discuss their mode of action, their clinical benefits, and the current challenges that will need to be addressed by the next-generation of anti-angiogenic drugs. We focus on the molecular structures and characteristics of each drug, including those approved only in China.
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Affiliation(s)
- Lei Wang
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Wang-Qing Liu
- CiTCoM, CNRS, INSERM, Université Paris Cité, Paris, France
| | | | - Bingnan Han
- Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Hongming Fang
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou, China
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10
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Fadaie M, Dianat-Moghadam H, Ghafouri E, Naderi S, Darvishali MH, Ghovvati M, Khanahmad H, Boshtam M, Makvandi P. Unraveling the potential of M13 phages in biomedicine: Advancing drug nanodelivery and gene therapy. ENVIRONMENTAL RESEARCH 2023; 238:117132. [PMID: 37714365 DOI: 10.1016/j.envres.2023.117132] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/05/2023] [Accepted: 09/12/2023] [Indexed: 09/17/2023]
Abstract
M13 phages possessing filamentous phage genomes offer the benefits of selective display of molecular moieties and delivery of therapeutic agent payloads with a tolerable safety profile. M13 phage-displayed technology for resembling antigen portions led to the discovery of mimetic epitopes that applied to antibody-based therapy and could be useful in the design of anticancer vaccines. To date, the excremental experiences have engaged the M13 phage in the development of innovative biosensors for detecting biospecies, biomolecules, and human cells with an acceptable limit of detection. Addressing the emergence of antibiotic-resistant bacteria, M13 phages are potent for packaging the programmed gene editing tools, such as CRISPR/Cas, to target multiple antimicrobial genes. Moreover, their display potential in combination with nanoparticles inspires new approaches for engineering targeted theragnostic platforms targeting multiple cellular biomarkers in vivo. In this review, we present the available data on optimizing the use of bacteriophages with a focus on the to date experiences with M13 phages, either as monoagent or as part of combination regimens in the practices of biosensors, vaccines, bactericidal, modeling of specific antigen epitopes, and phage-guided nanoparticles for drug delivery systems. Despite increasing research interest, a deep understanding of the underlying biological and genetic behaviors of M13 phages is needed to enable the full potential of these bioagents in biomedicine, as discussed here. We also discuss some of the challenges that have thus far limited the development and practical marketing of M13 phages.
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Affiliation(s)
- Mahmood Fadaie
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hassan Dianat-Moghadam
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Ghafouri
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shamsi Naderi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hossein Darvishali
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahsa Ghovvati
- Department of Radiological Sciences, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
| | - Hossein Khanahmad
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Maryam Boshtam
- Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Pooyan Makvandi
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, Zhejiang, China.
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11
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Liu S, Jia M, Dai R. Deciphering the tumour immune microenvironment of hepatocellular carcinoma. Scand J Immunol 2023; 98:e13327. [PMID: 38441331 DOI: 10.1111/sji.13327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/13/2023] [Accepted: 08/28/2023] [Indexed: 03/07/2024]
Abstract
Current treatments for hepatocellular carcinoma (HCC) are less effective and prone to recurrence after surgery, so it's needed to seek new ideas for its therapy. Tumour immune microenvironment (TME) is crucial for the pathogenesis, development and metastasis of HCC. Interactions between immune cells and tumour cells significantly impact responses to immunotherapies and patient prognosis. In recent years, immunotherapies for HCC have shown promising potential, but the response rate is still unsatisfactory. Understanding their cross-talks is helpful for selecting potential therapeutic targets, predicting immunotherapy responses, determining immunotherapy efficacy, identifying prognostic markers and selecting individualized treatment options. In this paper, we reviewed the research advances on the roles of immune cells and multi-omic research associated with HCC pathogenesis and therapy, and future perspectives on TME.
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Affiliation(s)
- Sha Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China
- Department of Pain, Daping Hospital, Army Medical University, Chongqing, China
| | - Man Jia
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China
| | - Rongyang Dai
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China
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12
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Azer SA, Alsharafi AA. Can pharmacy students use Wikipedia as a learning resource? Critical assessment of articles on chemotherapeutic drugs. ADVANCES IN PHYSIOLOGY EDUCATION 2023; 47:333-345. [PMID: 36951631 DOI: 10.1152/advan.00212.2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 02/17/2023] [Accepted: 03/11/2023] [Indexed: 06/18/2023]
Abstract
Pharmacy students tend to use Wikipedia as a quick resource of knowledge. This study aimed to evaluate the accuracy of content and readability level of Wikipedia articles on chemotherapeutics, using quality and readability tools. Using the British National Formulary (BNF-2018) and ClinicalTrials.gov, we identified 188 chemotherapeutic drugs. We randomly selected 100 drugs with an Excel randomization program. The English Wikipedia was searched for the selected 100 drugs, and prints of the identified articles were obtained. Readability was calculated with an online instrument (http://www.readabilityformulas.com/). Articles were independently scored by two researchers using the modified DISCERN tool for content assessment. The modified DISCERN scores had a median value of 24 [interquartile range (IQR) = 7.5]. Two articles (2%) had good quality (DISCERN score 36-40), thirty-eight (38%) were moderate (DISCERN 26-35), and sixty (60%) were poor in score (DISCERN ≤25). The articles covered drug indications and most side effects. However, the majority lacked information on the routes of administration, contraindications, pharmacokinetics, and mechanisms of action. We found a correlation between DISCERN scores and number of edits (P value = 0.00033, R2 = 0.1238). The number of references varied from 2 to 150 (median= 17, IQR = 17). Several problems were identified in the lists of references and citations. Most articles lacked tables and figures. The readability of the articles was 14.35 ± 3.13, consistent with the readability level of university students. In conclusion, the Wikipedia articles on chemotherapeutic drugs were not written for professional pharmacy students. Although they matched the expected readability level of university students, most were incomplete and lacked essential information.NEW & NOTEWORTHY Pharmacy students use Wikipedia as a quick resource of knowledge. However, Wikipedia articles are not written for professional pharmacy students. The study shows that although Wikipedia articles on chemotherapeutic drugs matched the expected readability level of university students, most needed to be completed and lacked essential information.
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Affiliation(s)
- Samy A Azer
- Department of Medical Education, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Aya A Alsharafi
- College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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13
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Villarruel-Melquiades F, Mendoza-Garrido ME, García-Cuellar CM, Sánchez-Pérez Y, Pérez-Carreón JI, Camacho J. Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma. World J Gastroenterol 2023; 29:2571-2599. [PMID: 37213397 PMCID: PMC10198058 DOI: 10.3748/wjg.v29.i17.2571] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/19/2023] [Accepted: 04/11/2023] [Indexed: 05/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumours worldwide. The mortality-to-incidence ratio is up to 91.6% in many countries, representing the third leading cause of cancer-related deaths. Systemic drugs, including the multikinase inhibitors sorafenib and lenvatinib, are first-line drugs used in HCC treatment. Unfortunately, these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance. Thus, novel pharmacological alternatives are urgently needed. For instance, immune checkpoint inhibitors have provided new approaches targeting cells of the immune system. Furthermore, monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients. In addition, drug combinations, including first-line treatment and immunotherapy, as well as drug repurposing, are promising novel therapeutic alternatives. Here, we review the current and novel pharmacological approaches to fight HCC. Preclinical studies, as well as approved and ongoing clinical trials for liver cancer treatment, are discussed. The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.
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Affiliation(s)
- Fernanda Villarruel-Melquiades
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico
| | - María Eugenia Mendoza-Garrido
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico
| | - Claudia M García-Cuellar
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Mexico City 14080, Mexico
| | - Yesennia Sánchez-Pérez
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Mexico City 14080, Mexico
| | - Julio Isael Pérez-Carreón
- Instituto Nacional de Medicina Genómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico
| | - Javier Camacho
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico
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14
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Sun H, Yang H, Mao Y. Personalized treatment for hepatocellular carcinoma in the era of targeted medicine and bioengineering. Front Pharmacol 2023; 14:1150151. [PMID: 37214451 PMCID: PMC10198383 DOI: 10.3389/fphar.2023.1150151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/24/2023] [Indexed: 05/24/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major global health burden, causing approximately 8.3 million deaths each year, and it is the third leading cause of cancer-related death worldwide, with a relative 5-year survival rate of around 18%. Due to the advanced stage of diagnosis in most patients, systemic treatment based on targeted therapy has become the only feasible option. Genomic studies have established a profile of molecular alterations in hepatocellular carcinoma with potentially actionable mutations, but these mutations have yet to be translated into clinical practice. The first targeted drug approved for systemic treatment of patients with advanced hepatocellular carcinoma was Sorafenib, which was a milestone. Subsequent clinical trials have identified multiple tyrosine kinase inhibitors, such as Lenvatinib, Cabozantinib, and Regorafenib, for the treatment of hepatocellular carcinoma, with survival benefits for the patient. Ongoing systemic therapy studies and trials include various immune-based combination therapies, with some early results showing promise and potential for new therapy plans. Systemic therapy for hepatocellular carcinoma is complicated by the significant heterogeneity of the disease and its propensity for developing drug resistance. Therefore, it is essential to choose a better, individualized treatment plan to benefit patients. Preclinical models capable of preserving in vivo tumor characteristics are urgently needed to circumvent heterogeneity and overcome drug resistance. In this review, we summarize current approaches to targeted therapy for HCC patients and the establishment of several patient-derived preclinical models of hepatocellular carcinoma. We also discuss the challenges and opportunities of targeted therapy for hepatocellular carcinoma and how to achieve personalized treatment with the continuous development of targeted therapies and bioengineering technologies.
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Affiliation(s)
| | - Huayu Yang
- *Correspondence: Huayu Yang, ; Yilei Mao,
| | - Yilei Mao
- *Correspondence: Huayu Yang, ; Yilei Mao,
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15
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Candido MF, Medeiros M, Veronez LC, Bastos D, Oliveira KL, Pezuk JA, Valera ET, Brassesco MS. Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario. Pharmaceutics 2023; 15:pharmaceutics15020664. [PMID: 36839989 PMCID: PMC9966033 DOI: 10.3390/pharmaceutics15020664] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 02/18/2023] Open
Abstract
Childhood cancer is considered rare, corresponding to ~3% of all malignant neoplasms in the human population. The World Health Organization (WHO) reports a universal occurrence of more than 15 cases per 100,000 inhabitants around the globe, and despite improvements in diagnosis, treatment and supportive care, one child dies of cancer every 3 min. Consequently, more efficient, selective and affordable therapeutics are still needed in order to improve outcomes and avoid long-term sequelae. Alterations in kinases' functionality is a trademark of cancer and the concept of exploiting them as drug targets has burgeoned in academia and in the pharmaceutical industry of the 21st century. Consequently, an increasing plethora of inhibitors has emerged. In the present study, the expression patterns of a selected group of kinases (including tyrosine receptors, members of the PI3K/AKT/mTOR and MAPK pathways, coordinators of cell cycle progression, and chromosome segregation) and their correlation with clinical outcomes in pediatric solid tumors were accessed through the R2: Genomics Analysis and Visualization Platform and by a thorough search of published literature. To further illustrate the importance of kinase dysregulation in the pathophysiology of pediatric cancer, we analyzed the vulnerability of different cancer cell lines against their inhibition through the Cancer Dependency Map portal, and performed a search for kinase-targeted compounds with approval and clinical applicability through the CanSAR knowledgebase. Finally, we provide a detailed literature review of a considerable set of small molecules that mitigate kinase activity under experimental testing and clinical trials for the treatment of pediatric tumors, while discuss critical challenges that must be overcome before translation into clinical options, including the absence of compounds designed specifically for childhood tumors which often show differential mutational burdens, intrinsic and acquired resistance, lack of selectivity and adverse effects on a growing organism.
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Affiliation(s)
- Marina Ferreira Candido
- Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
| | - Mariana Medeiros
- Regional Blood Center, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
| | - Luciana Chain Veronez
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
| | - David Bastos
- Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-901, SP, Brazil
| | - Karla Laissa Oliveira
- Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-901, SP, Brazil
| | - Julia Alejandra Pezuk
- Departament of Biotechnology and Innovation, Anhanguera University of São Paulo, UNIAN/SP, São Paulo 04119-001, SP, Brazil
| | - Elvis Terci Valera
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
| | - María Sol Brassesco
- Departament of Biotechnology and Innovation, Anhanguera University of São Paulo, UNIAN/SP, São Paulo 04119-001, SP, Brazil
- Correspondence: ; Tel.: +55-16-3315-9144; Fax: +55-16-3315-4886
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16
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Laface C, Fedele P, Maselli FM, Ambrogio F, Foti C, Molinari P, Ammendola M, Lioce M, Ranieri G. Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities. Cancers (Basel) 2022; 14:4028. [PMID: 36011021 PMCID: PMC9406380 DOI: 10.3390/cancers14164028] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/15/2022] [Accepted: 08/18/2022] [Indexed: 12/05/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver, accounting for 90% of all recorded cases. HCC is the third most common cause of cancer-related death, with a 5-year survival rate of just 3%. In the advanced stages, systemic treatments allow doctors to obtain clinical benefits, although the prognosis remains very poor. In the past few decades, new molecular targeted therapies against receptor tyrosine kinases have been developed and clinically evaluated. Sorafenib was the first oral tyrosine kinase inhibitor (TKI) approved for the treatment of advanced HCC in 2007. Subsequently, other TKIs, including Cabozantinib, Regorafenib, Lenvatinib, and vascular endothelial growth factor receptor (VEGFR) inhibitors such as Ramucirumab and VEGF inhibitors such as Bevacizumab have been approved as first- or second-line treatments. More recently, the combination of immune checkpoint inhibitors and VEGF inhibitors (Atezolizumab plus Bevacizumab) have been analyzed and approved for the treatment of advanced HCC. On the basis of the poor prognoses and the meager benefits deriving from the available systemic therapies, research into new treatments is extremely necessary. In this review, we focus on the available systemic therapies for advanced HCC, with a look toward the future.
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Affiliation(s)
- Carmelo Laface
- Medical Oncology, Dario Camberlingo Hospital, 72021 Francavilla Fontana, BR, Italy
| | - Palma Fedele
- Medical Oncology, Dario Camberlingo Hospital, 72021 Francavilla Fontana, BR, Italy
| | | | - Francesca Ambrogio
- Section of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari, 70124 Bari, Italy
| | - Caterina Foti
- Section of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari, 70124 Bari, Italy
| | | | - Michele Ammendola
- Department of Health Science, General Surgery, Medicine School of Germaneto, Magna Graecia University, 88100 Catanzaro, Italy
| | - Marco Lioce
- IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
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17
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Aghanejad A, Bonab SF, Sepehri M, Haghighi FS, Tarighatnia A, Kreiter C, Nader ND, Tohidkia MR. A review on targeting tumor microenvironment: The main paradigm shift in the mAb-based immunotherapy of solid tumors. Int J Biol Macromol 2022; 207:592-610. [PMID: 35296439 DOI: 10.1016/j.ijbiomac.2022.03.057] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 12/11/2022]
Abstract
Monoclonal antibodies (mAbs) as biological macromolecules have been remarked the large and growing pipline of the pharmaceutical market and also the most promising tool in modern medicine for cancer therapy. These therapeutic entities, which consist of whole mAbs, armed mAbs (i.e., antibody-toxin conjugates, antibody-drug conjugates, and antibody-radionuclide conjugates), and antibody fragments, mostly target tumor cells. However, due to intrinsic heterogeneity of cancer diseases, tumor cells targeting mAb have been encountered with difficulties in their unpredictable efficacy as well as variability in remission and durable clinical benefits among cancer patients. To address these pitfalls, the area has undergone two major evolutions with the intent of minimizing anti-drug responses and addressing limitations experienced with tumor cell-targeted therapies. As a novel hallmark of cancer, the tumor microenvironment (TME) is becoming the great importance of attention to develop innovative strategies based on therapeutic mAbs. Here, we underscore innovative strategies targeting TME by mAbs which destroy tumor cells indirectly through targeting vasculature system (e.g., anti-angiogenesis), immune system modulation (i.e., stimulation, suppression, and depletion), the targeting and blocking of stroma-based growth signals (e.g., cancer-associated fibroblasts), and targeting cancer stem cells, as well as, their effector mechanisms, clinical uses, and relevant mechanisms of resistance.
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Affiliation(s)
- Ayuob Aghanejad
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samad Farashi Bonab
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Sepehri
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Sadat Haghighi
- Yazd Diabetes Research Center, Shahid Sadoghi University of Medical Sciences, Yazd, Iran
| | - Ali Tarighatnia
- Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Christopher Kreiter
- Department of Anesthesiology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA
| | - Nader D Nader
- Department of Anesthesiology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA
| | - Mohammad Reza Tohidkia
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
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18
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Yao M, Yang JL, Wang DF, Wang L, Chen Y, Yao DF. Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma. World J Clin Cases 2022; 10:3321-3333. [PMID: 35611205 PMCID: PMC9048543 DOI: 10.12998/wjcc.v10.i11.3321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/10/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
The prevention, early discovery and effective treatment of patients with hepatocellular carcinoma (HCC) remain a global medical challenge. At present, HCC is still mainly treated by surgery, supplemented by vascular embolization, radio frequency, radiotherapy, chemotherapy and biotherapy. The application of multikinase inhibitor sorafenib, chimeric antigen receptor T cells, or PD-1/PD-L1 inhibitors can prolong the median survival of HCC patients. However, the treatment efficacy is still unsatisfactory due to HCC metastasis and postoperative recurrence. During the process of hepatocyte malignant transformation, HCC tissues can express and secrete many types of specific biomarkers, or oncogenic antigen molecules into blood, for example, alpha-fetoprotein, glypican-3, Wnt3a (one of the key signaling molecules in the Wnt/β-catenin pathway), insulin-like growth factor (IGF)-II or IGF-I receptor, vascular endothelial growth factor, secretory clusterin and so on. In addition, combining immunotherapy with non-coding RNAs might improve anti-cancer efficacy. These biomarkers not only contribute to HCC diagnosis or prognosis, but may also become molecular targets for HCC therapy under developing or clinical trials. This article reviews the progress in emerging biomarkers in basic research or clinical trials for HCC immunotherapy.
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Affiliation(s)
- Min Yao
- Research Center of Clinical Medicine & Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Jun-Ling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - De-Feng Wang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Ying Chen
- Department of Oncology, Affiliated Second Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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19
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Ansari MJ, Bokov D, Markov A, Jalil AT, Shalaby MN, Suksatan W, Chupradit S, AL-Ghamdi HS, Shomali N, Zamani A, Mohammadi A, Dadashpour M. Cancer combination therapies by angiogenesis inhibitors; a comprehensive review. Cell Commun Signal 2022; 20:49. [PMID: 35392964 PMCID: PMC8991477 DOI: 10.1186/s12964-022-00838-y] [Citation(s) in RCA: 104] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 02/03/2022] [Indexed: 02/06/2023] Open
Abstract
Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. Video abstract.
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Affiliation(s)
- Mohammad Javed Ansari
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia
| | - Dmitry Bokov
- Institute of Pharmacy, Sechenov First Moscow State Medical University, 8 Trubetskaya St., bldg. 2, Moscow, 119991 Russian Federation
- Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr., Moscow, 109240 Russian Federation
| | - Alexander Markov
- Tyumen State Medical University, Tyumen, Russian Federation
- Industrial University, Tyumen, Russian Federation
| | - Abduladheem Turki Jalil
- Faculty of Biology and Ecology, Yanka Kupala State University of Grodno, 230023 Grodno, Belarus
- College of Technical Engineering, The Islamic University, Najaf, Iraq
- Department of Dentistry, Kut University College, Kut, Wasit 52001 Iraq
| | - Mohammed Nader Shalaby
- Biological Sciences and Sports Health Department, Faculty of Physical Education, Suez Canal University, Ismailia, Egypt
| | - Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Supat Chupradit
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200 Thailand
| | - Hasan S. AL-Ghamdi
- Internal Medicine Department, Division of Dermatology, Albaha University, Al Bahah, Kingdom of Saudi Arabia
| | - Navid Shomali
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Zamani
- Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Mohammadi
- Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran
| | - Mehdi Dadashpour
- Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
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20
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Fan Y, Xue H, Zheng H. Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook. J Hepatocell Carcinoma 2022; 9:233-263. [PMID: 35388357 PMCID: PMC8977221 DOI: 10.2147/jhc.s358082] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/15/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) has emerged the culprit of cancer-related mortality worldwide with its dismal prognosis climbing. In recent years, ground-breaking progress has been made in systemic therapy for HCC. Targeted therapy based on specific signaling molecules, including sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab, has been widely used for advanced HCC (aHCC). Immunotherapies such as pembrolizumab and nivolumab greatly improve the survival of aHCC patients. More recently, synergistic combination therapy has boosted first-line (atezolizumab in combination with bevacizumab) and second-line (ipilimumab in combination with nivolumab) therapeutic modalities for aHCC. This review aims to summarize recent updates of systemic therapy relying on the biological mechanisms of HCC, particularly highlighting the approved agents for aHCC. Adjuvant and neoadjuvant therapy, as well as a combination with locoregional therapies (LRTs), are also discussed. Additionally, we describe the promising effect of traditional Chinese medicine (TCM) as systemic therapy on HCC. In this setting, the challenges and future directions of systemic therapy for HCC are also explored.
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Affiliation(s)
- Yinjie Fan
- College of Integrated Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China
- Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
| | - Hang Xue
- Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
| | - Huachuan Zheng
- Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
- Correspondence: Huachuan Zheng, Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China, Tel +86-0314-2279458, Fax +86-0314-2279458, Email
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21
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Choucair K, Kamran S, Saeed A. Clinical Evaluation of Ramucirumab for the Treatment of Hepatocellular Carcinoma (HCC): Place in Therapy. Onco Targets Ther 2022; 14:5521-5532. [PMID: 35002257 PMCID: PMC8721285 DOI: 10.2147/ott.s268309] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma remains one of the leading causes of death from cancer worldwide as most cases are diagnosed at an advanced disease stage. Ramucirumab, a human anti-VEGFR-2 monoclonal antibody, is approved as a monotherapy for the treatment of patients with hepatocellular carcinoma and α-fetoprotein levels ≥400 ng/mL previously treated with sorafenib. As most patients present with an advanced disease, patients with α-fetoprotein levels ≥400 ng/mL have an aggressive disease and a poor prognosis, making ramucirumab an important treatment option for this subgroup of patients. This article provides a comprehensive review of the clinical efficacy of ramucirumab as highlighted in the two major trials that lead to its approval. We also briefly review the agent pharmacologic properties, as well as its safety and toxicity profile, before discussing certain limitations and challenges associated with ramucirumab use. Finally, we review completed and ongoing clinical trials and focus on those involving ramucirumab-based combinations, namely with immune therapy.
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Affiliation(s)
- Khalil Choucair
- Department of Medicine, Kansas University School of Medicine, Wichita, KS, USA
| | - Syed Kamran
- Department of Medicine, Kansas University School of Medicine, Wichita, KS, USA
| | - Anwaar Saeed
- Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS, USA
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22
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Luengas-Martinez A, Paus R, Young HS. A novel personalised treatment approach for psoriasis: anti-VEGF-A therapy. Br J Dermatol 2021; 186:782-791. [PMID: 34878645 PMCID: PMC9313866 DOI: 10.1111/bjd.20940] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/01/2021] [Accepted: 12/04/2021] [Indexed: 12/25/2022]
Abstract
Chronic plaque psoriasis is an inflammatory skin disease in which genetic predisposition along with environmental factors lead to the development of the disease, which affects 2% of the UK’s population and is associated with extracutaneous morbidities and a reduced quality of life. A complex crosstalk between innate and adaptive immunity, the epithelia and the vasculature maintain the inflammatory milieu in psoriasis. Despite the development of promising treatment strategies, mostly targeting the immune system, treatments fail to fulfil every patient’s goals. Vascular endothelial growth factor‐A (VEGF‐A) mediates angiogenesis and is upregulated in the plaques and plasma of patients with psoriasis. Transgenic expression of VEGF‐A in experimental models led to the development of skin lesions that share many psoriasis features. Targeting VEGF‐A in in vivo models of psoriasis‐like inflammation resulted in disease clearance. Anti‐angiogenesis treatments are widely used for cancer and eye disease and there are clinical reports of patients treated with VEGF‐A inhibitors who have experienced Psoriasis Area and Severity Index improvement. Existing psoriasis treatments downregulate VEGF‐A and angiogenesis as part of their therapeutic effect. Pharmacogenetics studies suggest the existence of different genetic signatures within patients with psoriasis that correspond with different treatment responsiveness and disease severity. There is a subset of patients with psoriasis with an increased predisposition to produce high levels of VEGF‐A, who may be most likely to benefit from anti‐VEGF‐A therapy, offering an opportunity to personalize treatment in psoriasis. Anti‐VEGF‐A therapies may offer an alternative to existing anticytokine strategies or be complementary to standard treatments for the management of psoriasis.
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Affiliation(s)
- A Luengas-Martinez
- Centre for Dermatology Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
| | - R Paus
- Centre for Dermatology Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.,Dr. Philip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - H S Young
- Centre for Dermatology Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
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23
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Qing X, Xu W, Zong J, Du X, Peng H, Zhang Y. Emerging treatment modalities for systemic therapy in hepatocellular carcinoma. Biomark Res 2021; 9:64. [PMID: 34419152 PMCID: PMC8380325 DOI: 10.1186/s40364-021-00319-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 08/05/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has long been a major global clinical problem as one of the most common malignant tumours with a high rate of recurrence and mortality. Although potentially curative therapies are available for the early and intermediate stages, the treatment of patients with advanced HCC remains to be resolved. Fortunately, the past few years have shown the emergence of successful systemic therapies to treat HCC. At the molecular level, HCC is a heterogeneous disease, and current research on the molecular characteristics of HCC has revealed numerous therapeutic targets. Targeted agents based on signalling molecules have been successfully supported in clinical trials, and molecular targeted therapy has already become a milestone for disease management in patients with HCC. Immunotherapy, a viable approach for the treatment of HCC, recognizes the antigens expressed by the tumour and treats the tumour using the immune system of the host, making it both selective and specific. In addition, the pipeline for HCC is evolving towards combination therapies with promising clinical outcomes. More drugs designed to focus on specific pathways and immune checkpoints are being developed in the clinic. It has been demonstrated that some drugs can improve the prognosis of patients with HCC in first- or second-line settings, and these drugs have been approved by the Food and Drug Administration or are nearing approval. This review describes targeting pathways and systemic treatment strategies in HCC and summarizes effective targeted and immune-based drugs for patients with HCC and the problems encountered.
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Affiliation(s)
- Xin Qing
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Wenjing Xu
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Jingjing Zong
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Xuanlong Du
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Hao Peng
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Yewei Zhang
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
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24
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Novy Z, Janousek J, Barta P, Petrik M, Hajduch M, Trejtnar F. Preclinical evaluation of anti-VEGFR2 monoclonal antibody ramucirumab labelled with zirconium-89 for tumour imaging. J Labelled Comp Radiopharm 2021; 64:262-270. [PMID: 33818828 DOI: 10.1002/jlcr.3909] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 03/01/2021] [Accepted: 04/02/2021] [Indexed: 12/11/2022]
Abstract
The key factors participating in angiogenesis include vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), particularly VEGFR2. Angiogenesis suppression comprises the blocking of the VEGFR2 binding site by the monoclonal antibody ramucirumab (RAM). Our study focused on RAM radiolabelling with zirconium-89 along with subsequent in vitro and in vivo biological evaluation. RAM was conjugated with the bifunctional chelator p-SCN-Bn-deferoxamine (DFO) and subsequently radiolabelled with [89 Zr]Zr-oxalate. The binding affinity of [89 Zr]Zr-DFO-RAM to VEGFR2 was tested in vitro on prostate (PC-3) and ovary adenocarcinoma (SK-OV-3) cell lines. The positron emission tomography/computed tomography (PET/CT) imaging and ex vivo biodistribution experiments were performed in PC-3 and SK-OV-3 xenografted mice. The in vitro experiments revealed the preserved binding affinity of [89 Zr]Zr-DFO-RAM to VEGFR2. The obtained ex vivo biodistribution data showed the uptake in PC-3 and SK-OV-3 tumours at about 8.7 ± 0.2 and 12.1 ± 1.6%ID/g, respectively. The tumour-to-muscle ratio for 1, 3 and 6 days post injection was 3.9, 5.5 and 5.12 for PC-3 and 6.0, 8.0 and 8.82 for SK-OV-3 tumours, respectively. PET/CT images showed high radioactivity accumulation in the tumours starting already on the first day after tracer administration. The obtained results proved the potency of [89 Zr]Zr-DFO-RAM to target and image VEGFR2-positive tumours in vivo.
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Affiliation(s)
- Zbynek Novy
- Palacky University Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Olomouc, Czech Republic
| | - Jiri Janousek
- Faculty of Pharmacy in Hradec Kralove, Department of Pharmacognosy, Charles University, Hradec Kralove, Czech Republic
| | - Pavel Barta
- Faculty of Pharmacy in Hradec Kralove, Department of Biophysics and Physical Chemistry, Charles University, Hradec Kralove, Czech Republic
| | - Milos Petrik
- Palacky University Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Olomouc, Czech Republic
| | - Marian Hajduch
- Palacky University Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Olomouc, Czech Republic
| | - Frantisek Trejtnar
- Faculty of Pharmacy in Hradec Kralove, Department of Pharmacology and Toxicology, Charles University, Hradec Kralove, Czech Republic
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25
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Wang X, Ge Y, Shi M, Dai H, Liu W, Wang P. Protein kinase N1 promotes proliferation and invasion of liver cancer. Exp Ther Med 2021; 21:651. [PMID: 33968181 PMCID: PMC8097187 DOI: 10.3892/etm.2021.10083] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 03/22/2021] [Indexed: 12/24/2022] Open
Abstract
Protein kinase (PK) N1, also called PKC-related protein 1, participates in the proliferation, invasion and metastasis of various malignant tumors. However, the role of PKN1 in liver cancer remains to be elucidated. The present study investigated the expression of PKN1 using immunohistochemistry in surgical specimens from 36 patients and analyzed the correlation with VEGF, microvascular density (MVD), cell proliferation index (Ki67) and clinicopathological parameters. PKN1 was highly expressed in hepatocellular carcinoma (HCC) and was positively correlated with histological grading of HCC, Ki67 expression and MVD. PKN1 expression in moderately and poorly differentiated HCC was significantly higher compared with highly differentiated HCC. Expression of PKN1 was positively correlated with Ki67 and MVD, and Ki67 expression was positively correlated with MVD. The effects of PKN1 on proliferation, invasion and apoptosis of liver cancer cells were detected in vitro. Cell viability, migration and invasion were reduced and the apoptosis rate was significantly improved when PKN1 expression was silenced in liver cancer cells. Thus, PKN1 serves an important role in the development and progression of liver cancer. Inhibition of PKN1 activity may provide a promising therapeutic target for liver cancer.
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Affiliation(s)
- Xia Wang
- Department of Pathology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
| | - Yansong Ge
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
| | - Mingqi Shi
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
| | - Hanhan Dai
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
| | - Wei Liu
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
| | - Peiyuan Wang
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
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26
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Yang S, Chen C, Qiu Y, Xu C, Yao J. Paying attention to tumor blood vessels: Cancer phototherapy assisted with nano delivery strategies. Biomaterials 2020; 268:120562. [PMID: 33278682 DOI: 10.1016/j.biomaterials.2020.120562] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 11/17/2020] [Accepted: 11/19/2020] [Indexed: 12/18/2022]
Abstract
Cancer phototherapy has attracted increasing attention for its promising effectiveness and relative non-invasiveness. Over the past years, tremendous efforts have been made to develop better phototherapy strategies with various nano delivery systems. This review introduces cancer phototherapy strategies based on tumor blood vessels for improved therapeutic outcomes from the angle of direct tumor destruction and improved delivery process assisted with nano delivery designs. Latest directions and ideas of cancer phototherapy with translation potential are also discussed. Focusing on the double role of tumor vessels not only as an anti-tumor target but also as part of the delivery process, we highlight the crosstalk between photo-induced extensive effects and the complicated drug delivery process. Due to the heterogeneity of tumors, deeper investigations about the interconnection between tumor vessels and cancer phototherapy remain to be carried out. More delicate and intelligent nano delivery systems are expected to help realize the full potential of this therapeutic strategy.
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Affiliation(s)
- Shan Yang
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China
| | - Chen Chen
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China
| | - Yue Qiu
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China
| | - Cheng Xu
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China
| | - Jing Yao
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
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27
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Pu J, Wang J, Qin Z, Wang A, Zhang Y, Wu X, Wu Y, Li W, Xu Z, Lu Y, Tang Q, Wei H. IGF2BP2 Promotes Liver Cancer Growth Through an m6A-FEN1-Dependent Mechanism. Front Oncol 2020; 10:578816. [PMID: 33224879 PMCID: PMC7667992 DOI: 10.3389/fonc.2020.578816] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/07/2020] [Indexed: 12/22/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. N6-methyladenosine (m6A) plays an important role in posttranscriptional gene regulation. METTL3 and IGF2BP2 are key genes in the m6A signal pathway and have recently been shown to play important roles in cancer development and progression. In our work, higher METTL3 and IGF2BP2 expression were found in HCC tissues and were associated with a poor prognosis. In addition, IGF2BP2 overexpression promoted HCC proliferation in vitro and in vivo. Mechanistically, IGF2BP2 directly recognized and bound to the m6A site on FEN1 mRNA and enhanced FEN1 mRNA stability. Overall, our study revealed that METTL3 and IGF2BP2, acting as an oncogene, maintained FEN1 expression through an m6A-IGF2BP2-dependent mechanism in HCC cells, and indicated a potential biomarker panel for prognostic prediction in liver cancer.
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Affiliation(s)
- Jian Pu
- Department of General Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
| | - Jianchu Wang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
| | - Zebang Qin
- Graduate College of Youjiang Medical University for Nationalities, Guangxi, China
| | - Anmin Wang
- Graduate College of Youjiang Medical University for Nationalities, Guangxi, China
| | - Ya Zhang
- Graduate College of Youjiang Medical University for Nationalities, Guangxi, China
| | - Xianjian Wu
- Graduate College of Youjiang Medical University for Nationalities, Guangxi, China
| | - Yi Wu
- Graduate College of Youjiang Medical University for Nationalities, Guangxi, China
| | - Wenchuan Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
| | - Zuoming Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
| | - Yuan Lu
- Graduate College of Youjiang Medical University for Nationalities, Guangxi, China
| | - Qianli Tang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
| | - Huamei Wei
- Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
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28
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Alfaleh MA, Alsaab HO, Mahmoud AB, Alkayyal AA, Jones ML, Mahler SM, Hashem AM. Phage Display Derived Monoclonal Antibodies: From Bench to Bedside. Front Immunol 2020; 11:1986. [PMID: 32983137 PMCID: PMC7485114 DOI: 10.3389/fimmu.2020.01986] [Citation(s) in RCA: 162] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022] Open
Abstract
Monoclonal antibodies (mAbs) have become one of the most important classes of biopharmaceutical products, and they continue to dominate the universe of biopharmaceutical markets in terms of approval and sales. They are the most profitable single product class, where they represent six of the top ten selling drugs. At the beginning of the 1990s, an in vitro antibody selection technology known as antibody phage display was developed by John McCafferty and Sir. Gregory Winter that enabled the discovery of human antibodies for diverse applications, particularly antibody-based drugs. They created combinatorial antibody libraries on filamentous phage to be utilized for generating antigen specific antibodies in a matter of weeks. Since then, more than 70 phage–derived antibodies entered clinical studies and 14 of them have been approved. These antibodies are indicated for cancer, and non-cancer medical conditions, such as inflammatory, optical, infectious, or immunological diseases. This review will illustrate the utility of phage display as a powerful platform for therapeutic antibodies discovery and describe in detail all the approved mAbs derived from phage display.
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Affiliation(s)
- Mohamed A Alfaleh
- Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hashem O Alsaab
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Ahmad Bakur Mahmoud
- College of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia
| | - Almohanad A Alkayyal
- Department of Medical Laboratory Technology, University of Tabuk, Tabuk, Saudi Arabia
| | - Martina L Jones
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.,Australian Research Council Training Centre for Biopharmaceutical Innovation, The University of Queensland, Brisbane, QLD, Australia
| | - Stephen M Mahler
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.,Australian Research Council Training Centre for Biopharmaceutical Innovation, The University of Queensland, Brisbane, QLD, Australia
| | - Anwar M Hashem
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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29
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Zhao Y, Zhang YN, Wang KT, Chen L. Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy. Biochim Biophys Acta Rev Cancer 2020; 1874:188391. [PMID: 32659252 DOI: 10.1016/j.bbcan.2020.188391] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/06/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022]
Abstract
Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), is an emerging first-line therapy for hepatocellular carcinoma (HCC). Its application has changed the status of sorafenib as the only first-line TKI treatment for HCC for more than a decade. Evidence has shown that lenvatinib possesses antitumor proliferation and immunomodulatory activity in preclinical studies. In comparison, lenvatinib was non-inferior to sorafenib in overall survival (OS), and even shows superiority with regard to all the secondary efficacy endpoints. Immune-checkpoint inhibitors(ICIs)are now being incorporated into HCC treatment. Positive outcomes have been achieved in the combination of lenvatinib plus ICIs, bringing broader prospects for HCC. This review presents an overview on the therapeutic mechanisms and clinical efficacy of lenvatinib in HCC, and we discuss the future perspectives of lenvatinib in HCC management with focus on biomarker-guided precision medicine.
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Affiliation(s)
- Yan Zhao
- School of Life Sciences, Fudan University, Shanghai 200438, China.
| | - Ya-Ni Zhang
- School of Life Sciences, Fudan University, Shanghai 200438, China.
| | - Kai-Ting Wang
- School of Life Sciences, Fudan University, Shanghai 200438, China.
| | - Lei Chen
- International Cooperation Laboratory of Signal Transduction, Eastern Hepatobiliary Surgery Institute, China.
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30
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Dal Bo M, De Mattia E, Baboci L, Mezzalira S, Cecchin E, Assaraf YG, Toffoli G. New insights into the pharmacological, immunological, and CAR-T-cell approaches in the treatment of hepatocellular carcinoma. Drug Resist Updat 2020; 51:100702. [DOI: 10.1016/j.drup.2020.100702] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/06/2020] [Accepted: 04/13/2020] [Indexed: 02/07/2023]
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31
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Alfaleh MA, Alsaab HO, Mahmoud AB, Alkayyal AA, Jones ML, Mahler SM, Hashem AM. Phage Display Derived Monoclonal Antibodies: From Bench to Bedside. Front Immunol 2020. [PMID: 32983137 DOI: 10.3389/fimmu.2020.01986/bibtex] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2023] Open
Abstract
Monoclonal antibodies (mAbs) have become one of the most important classes of biopharmaceutical products, and they continue to dominate the universe of biopharmaceutical markets in terms of approval and sales. They are the most profitable single product class, where they represent six of the top ten selling drugs. At the beginning of the 1990s, an in vitro antibody selection technology known as antibody phage display was developed by John McCafferty and Sir. Gregory Winter that enabled the discovery of human antibodies for diverse applications, particularly antibody-based drugs. They created combinatorial antibody libraries on filamentous phage to be utilized for generating antigen specific antibodies in a matter of weeks. Since then, more than 70 phage-derived antibodies entered clinical studies and 14 of them have been approved. These antibodies are indicated for cancer, and non-cancer medical conditions, such as inflammatory, optical, infectious, or immunological diseases. This review will illustrate the utility of phage display as a powerful platform for therapeutic antibodies discovery and describe in detail all the approved mAbs derived from phage display.
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Affiliation(s)
- Mohamed A Alfaleh
- Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hashem O Alsaab
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Ahmad Bakur Mahmoud
- College of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia
| | - Almohanad A Alkayyal
- Department of Medical Laboratory Technology, University of Tabuk, Tabuk, Saudi Arabia
| | - Martina L Jones
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
- Australian Research Council Training Centre for Biopharmaceutical Innovation, The University of Queensland, Brisbane, QLD, Australia
| | - Stephen M Mahler
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
- Australian Research Council Training Centre for Biopharmaceutical Innovation, The University of Queensland, Brisbane, QLD, Australia
| | - Anwar M Hashem
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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