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Wei WJ, Hong YL, Deng Y, Wang GL, Qiu JT, Pan F. Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer: A review. World J Gastrointest Oncol 2024; 16:3397-3409. [PMID: 39171189 PMCID: PMC11334049 DOI: 10.4251/wjgo.v16.i8.3397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 05/31/2024] [Accepted: 06/21/2024] [Indexed: 08/07/2024] Open
Abstract
Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC.
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Affiliation(s)
- Wu-Jie Wei
- Department of Oncology, People's Hospital of Chongqing Hechuan, Chongqing 401520, China
| | - Ya-Li Hong
- Department of Cardiovascular, People's Hospital of Chongqing Hechuan, Chongqing 401520, China
| | - Yi Deng
- Intensive Care Unit, People's Hospital of Chongqing Hechuan, Chongqing 401520, China
| | - Guan-Liang Wang
- Department of Oncology, People's Hospital of Chongqing Hechuan, Chongqing 401520, China
| | - Jiang-Tao Qiu
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, Beijing 100084, China
| | - Fang Pan
- Department of Oncology, People's Hospital of Chongqing Hechuan, Chongqing 401520, China
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Wang LM, Zhang WW, Qiu YY, Wang F. Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer. World J Gastrointest Oncol 2024; 16:2781-2792. [PMID: 38994139 PMCID: PMC11236228 DOI: 10.4251/wjgo.v16.i6.2781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/06/2024] [Accepted: 04/10/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Gastric cancer is one of the most common malignant tumors in the world, and its occurrence and development involve complex biological processes. Iron death, as a new cell death mode, has attracted wide attention in recent years. However, the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear. AIM To explore the role of iron death in the development of gastric cancer, reveal its relationship with lipid peroxidation, and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer. METHODS The process of iron death in gastric cancer cells was simulated by cell culture model, and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry. The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology. In addition, a mouse model of gastric cancer was established, and the role of iron death in vivo was studied by histology and immunohistochemistry, and the level of lipid peroxidation was detected. These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer. RESULTS Iron death was significantly activated in gastric cancer cells, and at the same time, associated lipid peroxidation levels increased significantly. Through high-throughput sequencing analysis, it was found that iron death regulated the expression of several genes related to lipid metabolism. In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation. CONCLUSION This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer. The activation of iron death significantly increased lipid peroxidation levels, revealing its regulatory mechanism inside the cell.
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Affiliation(s)
- Lan-Mei Wang
- Department of Clinical Laboratory, Anqiu People's Hospital, Weifang 262123, Shandong Province, China
| | - Wei-Wei Zhang
- Department of Gastroenterology, Feicheng People's Hospital, Tai’an 271600, Shandong Province, China
| | - Ying-Yang Qiu
- Yong Loo Lin School of Medicine, National University of Singapore, 119077, Singapore
| | - Fang Wang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
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Kalapanida D, Zagouri F, Gazouli M, Tsiakou A, Zografos E, Dimitrakakis C, Marinopoulos S, Giannos A, Sergentanis TN, Kastritis E, Terpos E, Dimopoulos MA. Evaluation of MET T1010I and MET rs40239 single-nucleotide polymorphisms in triple-negative breast cancer: a case-control study. Onco Targets Ther 2019; 12:4195-4202. [PMID: 31213837 PMCID: PMC6549390 DOI: 10.2147/ott.s189329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 11/29/2018] [Indexed: 11/28/2022] Open
Abstract
Aim: The purpose of this study is to evaluate the role of MET T1010I and MET rs40239 as potential risk factor and/or prognostic markers in patients with triple-negative breast cancer (TNBC). Methods: 114 samples of DNA from paraffin-embedded breast normal tissues of patients with TNBC and 124 samples of healthy controls were collected and analyzed for MET T1010I and MET rs40239 polymorphisms. Results: MET T1010I CT genotype was associated with increased risk of TNBC in both univariate and multivariate analysis. The status of rs40239 was not associated with a higher risk for TNBC at either the univariate or the multivariate analysis. None of the examined polymorphisms was associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR=1.35, 95% CI: 0.31-5.97 for MET T1010I CT/TT vs CC; adjusted HR=1.78, 95% CI: 0.73-4.35 for rs40239 AG/GG vs AA). Conclusion: Our case-control study suggests that MET T1010I seems to be a risk factor for TNBC in the Caucasian Greek population, in contrast with MET rs40239, where no correlation was found.
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Affiliation(s)
- Despoina Kalapanida
- Department of Clinical Therapeutic, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Flora Zagouri
- Department of Clinical Therapeutic, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, University of Athens School of Medicine and Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
| | - Andriani Tsiakou
- First Department of Dermatology, Syggros Hospital, University of Athens School of Medicine, Athens, Greece
| | - Eleni Zografos
- Department of Basic Medical Sciences, Laboratory of Biology, University of Athens School of Medicine and Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
| | - Constantine Dimitrakakis
- Department of Obstetrics and Gynaecology, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Spyridon Marinopoulos
- Department of Obstetrics and Gynaecology, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Aris Giannos
- Department of Obstetrics and Gynaecology, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Theodoros N Sergentanis
- Department of Clinical Therapeutic, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Efstathios Kastritis
- Department of Clinical Therapeutic, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
| | - Evangelos Terpos
- Department of Clinical Therapeutic, Alexandra Hospital, Medical School, University of Athens, Athens, Greece
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Wang Q, Yu X, Li Q, Qin L, Tan S, Zeng X, Qiu X, Tang B, Jin J, Liao W, Qiu M, Tan L, He G, Li X, He S, Yu H. Association between miR-199a rs74723057 and MET rs1621 polymorphisms and the risk of hepatocellular carcinoma. Oncotarget 2018; 7:79365-79371. [PMID: 27813498 PMCID: PMC5346720 DOI: 10.18632/oncotarget.13033] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 10/21/2016] [Indexed: 12/14/2022] Open
Abstract
MicroRNAs (miRNAs) can regulate gene expression at post-transcriptional levels, thereby influence cancer risk. The aim of the current study is to investigate association between miR-199a rs74723057 and MET rs1621 and HCC risk in 1032 HCC patients and 1060 cancer-free controls. These two SNPs were genotyped by using the Agena MassARRAY genotyping system. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to assess the strength of the associations. We found that compared with the wild-type AA genotype of MET rs1621, the variant GG genotype was associated with a decreased risk for HCC (OR = 0.24, 95% CI = 0.06–0.96, P = 0.043). No association between miR-199a rs74723057 and HCC risk was observed. In addition, an interaction effect on HCC risk between the selected two SNPs was found. Among those who carried the CG/GG genotypes of miR-199a rs74723057, those who carried the GG genotype of MET rs1621 had a reduced risk of HCC, when compared with those who carried the AG/AA genotypes of MET rs1621 (OR = 0.15, 95% CI = 0.03~0.73, P for interaction = 0.018). Our results suggest that MET rs1621 polymorphism, alone and combined with miR-199a rs74723057, may influence susceptibility to HCC. Further large-scale association studies and functional studies are needed to validate our findings.
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Affiliation(s)
- Qianqian Wang
- Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
| | - Xiangyuan Yu
- Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
| | - Qiang Li
- Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
| | - Linyuan Qin
- Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
| | - Shengkui Tan
- Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
| | - Xiaoyun Zeng
- Department of Epidemiology and Health Statistics, Guangxi Medical University, Nanning 530021, China
| | - Xiaoqiang Qiu
- Department of Epidemiology and Health Statistics, Guangxi Medical University, Nanning 530021, China
| | - Bo Tang
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Junfei Jin
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Weijia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Moqin Qiu
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Lijun Tan
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Gaofeng He
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Xiaomei Li
- Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
| | - Songqing He
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin 541001, China
| | - Hongping Yu
- Department of Epidemiology and Health Statistics, Guangxi Medical University, Nanning 530021, China.,Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China
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Narita Y, Muro K. Challenges in molecular targeted therapy for gastric cancer: considerations for efficacy and safety. Expert Opin Drug Saf 2017; 16:319-327. [PMID: 27976952 DOI: 10.1080/14740338.2017.1273348] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION The Cancer Genome Atlas Research Network recently proposed a molecular classification for gastric cancer (GC) into four subtypes based on comprehensive evaluation. While the mechanisms of molecular targeted therapies in GC were confirmed by multiple clinical studies, only a limited number of therapeutics for GC have been approved to date. Areas covered: In this systematic review of the available literature, we discuss the completed and ongoing clinical trials of molecular targeted therapies in patients with GC, with a focus on their efficacy and safety profiles. Expert opinion: Results of recent studies clearly demonstrated that trastuzumab and ramucirumab, monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), respectively, improved overall survival (OS) in GC with manageable safety profiles. Careful surveillance of ongoing clinical trials and timely profiling and monitoring of genetic signatures are imperative to establish a strong foundation for precision medicine in GC.
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Affiliation(s)
- Yukiya Narita
- a Department of Clinical Oncology , Aichi Cancer Center Hospital , Nagoya , Japan
| | - Kei Muro
- a Department of Clinical Oncology , Aichi Cancer Center Hospital , Nagoya , Japan
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Inokuchi M, Otsuki S, Fujimori Y, Sato Y, Nakagawa M, Kojima K. Clinical significance of MET in gastric cancer. World J Gastrointest Oncol 2015; 7:317-327. [PMID: 26600931 PMCID: PMC4644854 DOI: 10.4251/wjgo.v7.i11.317] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 04/06/2015] [Accepted: 08/28/2015] [Indexed: 02/05/2023] Open
Abstract
Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.
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Vasconcelos AC, Wagner VP, Meurer L, Vargas PA, de Souza LB, Fonseca FP, Squarize CH, Castilho RM, Martins MD. Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 120:238-47. [PMID: 26117810 DOI: 10.1016/j.oooo.2015.04.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 02/11/2015] [Accepted: 04/08/2015] [Indexed: 01/29/2023]
Abstract
OBJECTIVE The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters. STUDY DESIGN We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed. RESULTS Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001). CONCLUSIONS The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.
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Affiliation(s)
- Artur Cunha Vasconcelos
- Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Vivian Petersen Wagner
- Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Luise Meurer
- Department of Pathology, Hospital de Clínicas de Porto Alegre (HCPA/UFRGS), Porto Alegre, Rio Grande do Sul, RS, Brazil
| | - Pablo Agustin Vargas
- Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Lélia Batista de Souza
- Department of Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil
| | - Felipe Paiva Fonseca
- Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Cristiane Helena Squarize
- Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Rogerio Moraes Castilho
- Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Manoela Domingues Martins
- Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
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Zhang Y, Jain RK, Zhu M. Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment. Biomedicines 2015; 3:149-181. [PMID: 28536405 PMCID: PMC5344234 DOI: 10.3390/biomedicines3010149] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 02/25/2015] [Accepted: 03/03/2015] [Indexed: 12/31/2022] Open
Abstract
The hepatocyte growth factor (HGF): MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents-either as therapeutic proteins or small molecules that target the HGF/MET pathway-have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.
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Affiliation(s)
- Yilong Zhang
- Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
| | - Rajul K Jain
- Kite Pharma, Inc., 2225 Colorado Avenue, Santa Monica, CA 90404, USA.
| | - Min Zhu
- Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
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Ning L, Yu Y, Liu X, Ai L, Zhang X, Rao W, Shi J, Sun H, Yu Q. Association Analysis of MET Gene Polymorphism with Papillary Thyroid Carcinoma in a Chinese Population. Int J Endocrinol 2015; 2015:405217. [PMID: 26649038 PMCID: PMC4662967 DOI: 10.1155/2015/405217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 10/16/2015] [Accepted: 10/27/2015] [Indexed: 01/22/2023] Open
Abstract
To investigate the association of MET SNPs with gender disparity in thyroid tumors, as well as the metastasis and prognosis of patients, 858 patients with papillary thyroid carcinoma (PTC), 556 patients with nodular goiter, and 896 population-based normal controls were recruited. The genotyping of MET SNPs was carried out using the Sequenom MassARRAY system. The distribution of MET SNPs (rs1621 and rs6566) was different among groups. Gender stratification analysis revealed a significant association between the rs1621 genotype and PTC in female patients (P = 0.037), but not in male patients (P > 0.05). For female patients, the rs1621 AG genotype was significantly higher in patients with PTC than in normal controls (P = 0.01) and revealed an increasing risk of PTC (OR: 1.465, 95% CI: 1.118-1.92). However, association analysis of the rs1621 genotype with metastasis and prognosis revealed no significant correlation in both male and female patients. The findings of our study showed that polymorphism of SNP locus rs1621 in MET gene may be associated with gender disparity in PTC. Higher AG genotypes in rs1621 were correlated with PTC in female patients, but not in male patients.
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Affiliation(s)
- Lifeng Ning
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
- National Research Institute for Family Planning, Beijing 100081, China
| | - Yaqin Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
| | - Xiaoli Liu
- Jilin Provincial Key Laboratory of Surgical Translational Medicine, Department of Thyroid and Parathyroid Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Lizhe Ai
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
| | - Xin Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
| | - Wenwang Rao
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
| | - Jieping Shi
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
| | - Hui Sun
- Jilin Provincial Key Laboratory of Surgical Translational Medicine, Department of Thyroid and Parathyroid Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Qiong Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
- *Qiong Yu:
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Abstract
INTRODUCTION The mesenchymal-epithelial transition (MET) protein is the only known receptor for hepatocyte growth factor and has recently been identified as a novel promising target in several human cancers, including NSCLC. Activation of the MET signaling pathway can occur via different mechanisms. A number of compounds targeting MET have been evaluated in clinical trials, and recent clinical data have begun to afford some insight into the tumor types and patient populations that might benefit from treatment with MET pathway inhibitors. AREAS COVERED We review recent publications and information disclosed at public conferences and summarize the epidemiology of dysregulation of MET signaling, and the associations thereof with other driver genes and therapeutic inhibitors useful to treat NSCLC. EXPERT OPINION The MET pathway is emerging as a target for advanced NSCLC that is either resistant to EGFR tyrosine kinase inhibitors or that arises de novo. MET inhibitors currently being evaluated in clinical trials have yielded compelling evidence of clinical activities when used to treat various solid tumors, especially NSCLC. Remaining challenges are the identification of patient populations who might benefit from the use of MET inhibitors, and the most effective diagnostic methods for such patients.
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Affiliation(s)
- Anna Li
- Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Science , 106 Zhongshan 2nd Road, Guangzhou 510080 , PR China +86 20 83877855 ; +86 20 83827712 ;
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