Trastuzumab (TRZ) is the first drug used to treat HER2-positive breast cancer, but some patients become resistant to it because of the PI3K/Akt pathway and other pathways that counteract it. TRZ, in conjunction with other therapeutic agents, is needed to overcome resistance. α-chaconine (CHA), a glycoalkaloid from the Solanaceae family, can suppress lung cancer cell proliferation in vitro by inhibiting PI3K/Akt signaling, one of the key regulatory pathways in TRZ resistance.

This study used integrative bioinformatics analysis to screen for possible targets of CHA that can help fight breast cancer that is resistant to TRZ. In vitro experiments were used to confirm the target genes using TRZ-resistant HCC-1954 (HCC-TRZ) cells for cytotoxicity, gene expression studies, and enzymatic assay.

We identified several potential target genes of CHA, including EGFR, VEGF, ACHE, and ADORA. We generated HCC1954-TRZ cells, which showed an increase in cell viability after sequential treatment of the parental HCC1954 cells with TRZ. Further experiments showed the high sensitivity of HCC-TRZ toward TRZ when TRZ was combined with CHA. The combination of CHA and TRZ significantly increased the mRNA expression levels of various genes compared to a single TRZ treatment. Additionally, CHA alone and combined with CHA-TRZ inhibited acetylcholinesterase (AChE) activity in HCC-TRZ cells.

CHA increased the sensitivity of HCC-TRZ cells to TRZ by targeting several potential target genes and AChE activity. This study highlights the potential of using CHA in combination with TRZ to overcome TRZ resistance in HER2+ breast cancer cells.

There has been an increase in the use of molecular probe diagnostic techniques for lung cancer, and magnetic resonance imaging (MRI) offers specific advantages for diagnosing pulmonary carcinoma. Furthermore, advancements in near-infrared II (NIR-II) fluorescence have provided a new method for precise intraoperative tumor resection. However, few probes combine preoperative diagnosis with intraoperative imaging. This study aims to fill this research void by employing a dual-modal probe that targets the epidermal growth factor receptor for MR and NIR-II imaging, enabling the preoperative diagnosis of lung cancer using MRI and precise intraoperative tumor localization using NIR-II with a single probe. The imaging effects and targeting ability of the probe were confirmed in cell lines, mouse models, and clinical samples. The MR signal decreased within 24 h in the patient-derived xenograft mouse model. The average signal-to-background ratio of NIR-II reached 3.98 ± 0.27. The clinical sample also showed a decrease in the T2 signal using MRI, and the NIR-II optical signal-to-background ratio was 3.29. It is expected that this probe can improve the diagnostic rate of lung cancer using MRI and enable precise intraoperative tumor resection using NIR-II.

Increased stemness of cancer cells exacerbates radioresistance, thereby greatly limiting the efficacy of radiotherapy. In order to study the changes in cancer cell stemness during radiotherapy, we established a radioresistance model of human non-small cell lung cancer A549 cells and obtained A549 radioresistant cells (A549-RR). We sampled the cells at different time points during the modeling process and investigated the heterogeneity of each group of cells using single-cell sequencing. Cells in the early stages of fractionated irradiation were found to be significantly up-regulated in stemness, and a subpopulation of cells producing this response was screened and referred to as "radiation-induced stemness-responsive cancer cells". They were undergoing stemness response, energy metabolism reprogramming, and progressively differentiating into cells with more diverse and malignant phenotypes in order to attenuate the killing effect of radiation. Furthermore, we demonstrated that such responses might be driven by the activation of the EGFR-Hippo signaling pathway axis, which also plays a crucial role in the development of radioresistance. Our study reveals the dynamic evolution of cell subpopulation in cancer cells during fractionated radiotherapy; the early stage of irradiation can determine the destiny of the radiation-induced stemness-responsive cancer cells. The activation of stemness-like phenotypes during the development of radioresistance is not the result of dose accumulation but occurs during the early stage of radiotherapy with relatively low-dose irradiation. The degree of the radiation-induced stemness response of cancer cells mediated by the EGFR-Hippo signaling pathway might be a potential predictor of the efficacy of radiotherapy and the development of radioresistance.

Periocular squamous cell carcinoma (SCC) is relatively rare and presents unique anatomic considerations due to proximity to the eye and risk to ocular structures associated with high-dose radiation therapy or radical surgery. We present our observations in patients with periocular SCC treated with immune checkpoint inhibitor (ICI) therapy in an effort to decrease surgical morbidity or avoid high-dose radiation therapy.

Retrospective review of patients with orbital, conjunctival, or periocular SCC who were treated with ICI either in the neoadjuvant setting prior to surgery or for treatment of perineural spread in the orbit/skull base.

Twelve men and 5 women with orbital (n = 6), conjunctival (n = 5), or lacrimal sac/duct (n = 2) SCC, or SCC with perineural spread (n = 4) were treated with ICI (cemiplimab or pembolizumab) either as single drug (n = 9) or combined with chemotherapy (n = 8). Overall, 5 patients achieved complete response, 8 patients achieved partial response, and 4 patients achieved stable disease, using the response evaluation criteria in solid tumors (RECIST) criteria. The objective response rate was 76.5%. In 12 patients ICI was used in the neoadjuvant setting prior to surgery. In 4 patients with perineural spread and unresectable disease, ICI was used to avoid high-dose radiation therapy. One additional patient with conjunctival SCC with nodal metastasis was treated with ICI alone and achieved a dramatic complete response and has thus far managed to avoid surgery altogether.

ICI either as single drug or in combination with chemotherapy has a high response rate in patients with periocular SCC. Future prospective trials should aim to correlate molecular data with response.

Treatment-related skin reactions (TRSRs) induced by enfortumab vedotin (EV) targeting nectin-4 are among the most common adverse events. However, their association with survival and treatment response is poorly understood.

We retrospectively identified patients who received EV from December 2021 to April 2023 at Nagoya University Hospital and its affiliated facilities and extracted clinical data from their medical records. We evaluated cancer-specific survival (CSS) and progression-free survival (PFS) as survival outcomes and overall response rate (ORR) and disease control rate (DCR) as treatment responses between patients with and without TRSRs.

In total, 67 eligible patients were identified. Thirty-four patients experienced TRSRs, and the remaining 33 did not experience TRSRs. The median follow-up period was 8 months. Patients in the TRSRs group demonstrated significantly longer median CSS (15 vs. 8 months; p = 0.003) and median PFS (10 vs. 5 months; p < 0.001) than the non-TRSRs. Regarding treatment response, the patients in the TRSRs group showed a favorable, albeit nonsignificant, treatment response trend compared with those in the non-TRSRs group (ORR, 73.5% vs. 51.5%; p = 0.107; DCR, 91.2 % vs. 81.8%; p = 0.444).

Patients with TRSRs demonstrated more prolonged survival and superior treatment responses to EV treatment. The role of TRSR as a surrogate marker of EV's efficacy should be further explored in prospective and sufficiently powered studies.

Targeted protein degradation (TPD) has emerged as a significant therapeutic approach for a variety of diseases, including cancer. Advances in TPD techniques, such as molecular glue (MG) and lysosome-dependent strategies, have shown substantial progress since the inception of the first PROTAC in 2001. The PROTAC methodology represents the forefront of TPD technology, with ongoing evaluation in more than 20 clinical trials for the treatment of diverse medical conditions. Two prominent PROTACs, ARV-471 and ARV-110, are currently undergoing phase III and II clinical trials, respectively. Traditional PROTACs are encountering obstacles such as limited binding affinity and a restricted range of E3 ligase ligands for facilitating the protein of interest (POI) degradation. Covalent medicines offer the potential to enhance PROTAC efficacy by enabling the targeting of previously considered "undruggable" shallow binding sites. Strategic alterations allow PROTAC to establish covalent connections with particular target proteins, including Kirsten rat sarcoma viral oncogene homolog (KRAS), Bruton's tyrosine kinase (BTK), epidermal growth factor receptor (EGFR), as well as E3 ligases such as DDB1 and CUL4 associated factor 16 (DCAF16) and Kelch-like ECH-associated protein 1 (Keap1). The concept of covalent degradation has also been utilized in various new forms of degraders, including covalent molecule glue (MG), in-cell click-formed proteolysis targeting chimera (CLIPTAC), HaloPROTAC, lysosome-targeting chimera (LYTAC) and GlueTAC. This review focuses on recent advancements in covalent degraders beyond covalent PROTACs and examines obstacles and future directions pertinent to this field.

The epidermal growth factor receptor (EGFR) governs pivotal signaling pathways in cell proliferation and survival, with mutations implicated in numerous cancers. The organization of EGFR on the plasma membrane (PM) is influenced by the lipids and the cortical actin (CA) cytoskeleton. Despite the presence of a putative actin-binding domain (ABD) spanning 13 residues, a direct interaction between EGFR and CA has not been definitively established. While disrupting the cytoskeleton can impact EGFR behavior, suggesting a connection, the influence of the static actin cytoskeleton has been found to be indirect. Here, we investigate the potential interaction between EGFR and CA, as well as the extent to which CA regulates EGFR's distribution on the PM using SRRF'n'TIRF, a spatiotemporal super-resolution microscopy technique that provides sub-100 nm resolution and ms-scale dynamics from the same data set. To label CA, we constructed PMT-mEGFP-F-tractin, which combines an inner leaflet targeting domain PMT, fluorescent probe mEGFP, and the actin-binding protein F-tractin. In addition to EGFR-mEGFP, we included two control constructs: 1) an ABD deletion mutant, EGFRΔABD-mEGFP serving as a negative control and 2) EGFR-mApple-F-tractin, where F-tractin is fused to the C-terminus of EGFR-mApple, serving as the positive control. We find that EGFR-mEGFP and EGFRΔABD-mEGFP show similar membrane dynamics, implying that EGFR-mEGFP dynamics and organization are independent of CA. EGFR dynamics show CA dependence when F-tractin is anchored to the cytoplasmic tail. Together, our results demonstrate that EGFR does not directly interact with the CA in its resting and activated state.

Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.

We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.

In vitro measurements of PIT dose responses revealed that although low light doses (<10 J/cm2) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response.

There is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.

Monoclonal antibodies (mAbs) are being used to prevent, detect, and treat a broad spectrum of malignancies and infectious and autoimmune diseases. Over the past few years, the market for mAbs has grown exponentially. They have become a significant part of many pharmaceutical product lines, and more than 250 therapeutic mAbs are undergoing clinical trials. Ever since the advent of hybridoma technology, antibody-based therapeutics were realized using murine antibodies which further progressed into humanized and fully human antibodies, reducing the risk of immunogenicity. Some of the benefits of using mAbs over conventional drugs include a drastic reduction in the chances of adverse reactions, interactions between drugs, and targeting specific proteins. While antibodies are very efficient, their higher production costs impede the process of commercialization. However, their cost factor has been improved by developing biosimilar antibodies, which are affordable versions of therapeutic antibodies. Along with biosimilars, innovations in antibody engineering have helped to design bio-better antibodies with improved efficacy than the conventional ones. These novel mAb-based therapeutics are set to revolutionize existing drug therapies targeting a wide spectrum of diseases, thereby meeting several unmet medical needs. In the future, mAbs generated by applying next-generation sequencing (NGS) are expected to become a powerful tool in clinical therapeutics. This article describes the methods of mAb production, pre-clinical and clinical development of mAbs, approved indications targeted by mAbs, and novel developments in the field of mAb research.

Biomaterials have potential applications in the treatment of myocardial infarction (MI). These biomaterials have the ability to mechanically support the ventricular wall and to modulate the inflammatory, metabolic, and local electrophysiological microenvironment. In addition, they can play an equally important role in promoting angiogenesis, which is the primary prerequisite for the treatment of MI. A variety of biomaterials are known to exert pro-angiogenic effects, but the pro-angiogenic mechanisms and functions of different biomaterials are complex and diverse, and have not yet been systematically described. This review will focus on the pro-angiogenesis of biomaterials and systematically describe the mechanisms and functions of different biomaterials in promoting angiogenesis in MI.

There are limited conventional chemotherapy options for biliary tract cancers (BTCs), a heterogenous group of lethal, rare malignancies. The receptor tyrosine kinase (RTK) is closely associated with the progression of human malignancies through the regulation of cell cycle. Overexpression or amplification of RTKs has been investigated as a potential biomarker and therapeutic target in BTC; herein, we investigate the value of such interventions.

Overexpression of RTK proteins was examined by immunohistochemistry in 193 BTC samples, of which 137 were gallbladder carcinoma, 29 were perihilar cholangiocarcinoma, and 27 were intrahepatic cholangiocarcinoma. Silver in situ hybridization of MET and HER2 was performed to assess gene amplification.

In the entire cancer group, gallbladder, perihilar, and intrahepatic, MET amplification rates were 15.7%, 19.0%, 3.4%, and 14.8%, respectively, and of HER2 amplification rates were 22.4%, 27.2%, 17.2%, and 3.7%, respectively. MET and HER2 protein expressions were significantly correlated with their gene amplification status. RTKs were significantly associated with adverse clinicopathologic features such as advanced pT category and lymph node metastasis. Overall survival was significantly shorter in MET-amplified (P = .024) and EGFR-overexpressed cases (P = .045). Recurrence-free survival was significantly correlated with HER2-amplified (P = .038) and EGFR-overexpressed cases (P = .046) in all patient groups. Overall and recurrence-free survival were significantly shorter in patients who were double positive for HER2 and EGFR.

Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs.

Throughout the reported applications of EGFR inhibitors, it is usually employed with HDAC or other targets to design multi-target inhibitors for cancer treatment. In this paper, we designed a drug conjugate that targeted EGFR&HER2 and had inhibitory activity of NAMPT simultaneously. Compound 20c significantly inhibited the EGFR&HER2 and NAMPT enzyme activities, and had comparable or even higher anti-proliferative activity than lapatinib in various cancer cells with over-expressed EGFR and HER2. Importantly, 20c was expected to increase sensitivity to EGFR inhibitor-resistant cells. In Osimertinib-resistant cells (NCI-1975 cells with the L858R/T790M/C797S triple mutation and Ba/F3 cells with the Del19/T790M/C797S triple mutation), the anti-proliferative activity of compound 20c was increased by more than twofold compared with Osimertinib, so as to obtain better curative effect. This strategy is a promising method of embedding multiple pharmacophores into a single molecule, which lays a good foundation for the design and synthesis of small molecule drug conjugates with strong targeting ability and high cytotoxicity.

Ovarian cancer is the most lethal gynecological cancer, with a survival rate of approximately 40% at five years from the diagno. The first-line treatment consists of cytoreductive surgery combined with chemotherapy (platinum- and taxane-based drugs). To date, the main prognostic factor is related to the complete surgical resection of tumor lesions, including occult micrometastases. The presence of minimal residual diseases not detected by visual inspection and palpation during surgery significantly increases the risk of disease relapse. Intraoperative fluorescence imaging systems have the potential to improve surgical outcomes. Fluorescent tracers administered to the patient may support surgeons for better real-time visualization of tumor lesions during cytoreductive procedures. In the last decade, consistent with the discovery of an increasing number of ovarian cancer-specific targets, a wide range of fluorescent agents were identified to be employed for intraoperatively detecting ovarian cancer. Here, we present a collection of fluorescent probes designed and developed for fluorescence-guided ovarian cancer surgery. Original articles published between 2011 and November 2022 focusing on fluorescent probes, currently under preclinical and clinical investigation, were searched in PubMed. The keywords used were targeted detection, ovarian cancer, fluorescent probe, near-infrared fluorescence, fluorescence-guided surgery, and intraoperative imaging. All identified papers were English-language full-text papers, and probes were classified based on the location of the biological target: intracellular, membrane, and extracellular.

Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility.

Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan-Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes.

A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10-7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10-7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10-7 and DFS: p = 1.21 × 10-7) databases.

We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.

In-vitro anticancer activity has been conducted on MCF7 cells, and mammary carcinoma has been induced in Wistar rats by introduction of 7, 12-Dimethylbenz(a)anthracene (DMBA), which was sustained for 24 weeks. Histopathology, immunohistochemistry, cell proliferation study and apoptosis assay via TUNEL method was conducted to evaluate an antineoplastic activity of temozolomide in rat breast tissue.

IC50 value of temozolomide in MCF7 cell has been obtained as 103 μM, which demonstrated an initiation of apoptosis. The temozolomide treatment facilitated cell cycle arrest in G2/M and S phase dose dependently. The treatment with temozolomide suggested decrease of the hyperplastic abrasions and renovation of the typical histological features of mammary tissue. Moreover, temozolomide therapy caused the downregulation of epidermal growth factor receptor, extracellular signal-regulated kinase, and metalloproteinase-1 expression and upstream of p53 and caspase-3 proliferation to indicate an initiation of apoptotic events.

The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti-EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products-derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.

We describe our findings in patients with locally advanced lacrimal sac and nasolacrimal duct (NLD) carcinoma who received neoadjuvant systemic therapy.

We identified patients with locally advanced primary lacrimal sac/NLD carcinoma treated with neoadjuvant systemic intravenous therapy at our institution during 2017-2019.

The study included seven patients, four men and three women; the mean age was 60.4 years (range: 43-76). All patients had locally advanced disease with significant orbital soft tissue invasion with or without skull base invasion making eye-sparing surgery not feasible as an initial step. Three patients had poorly differentiated squamous cell carcinoma; two, invasive carcinoma with basaloid and squamous features; one, high-grade carcinoma with features suggestive of sebaceous differentiation; and one, undifferentiated carcinoma. The neoadjuvant regimens were cisplatin and docetaxel (n = 1); carboplatin and docetaxel (n = 1); paclitaxel and cetuximab (n = 1); carboplatin, paclitaxel, and cetuximab (EGFR inhibitor) (n = 2); cisplatin, docetaxel, and pembrolizumab (anti-PD-1 immunotherapy) (n = 1); and carboplatin, paclitaxel, and pembrolizumab (n = 1). All patients had radiologic disease regression, and one patient had radiologic near-complete response. After neoadjuvant therapy, all patients underwent wide local excision and adjuvant concurrent chemoradiation. Two patients had a complete pathologic response. At a median follow-up period of 13 months after chemoradiation (range, 8-54 months), all patients were alive without evidence of disease. One patient had nodal metastasis treated with lymph node dissection and adjuvant chemoradiation.

Neoadjuvant systemic therapy can shrink tumors in patients with locally advanced primary lacrimal sac/NLD carcinoma with orbital or skull base invasion.

Breast cancer ranks first among gynecological cancer in India. It is associated with urbanization, changes in lifestyle and obesity. Hormones also play a crucial role in the development of breast cancer. Steroid hormones play critical role in development of breast cancer.

Breast cancer is caused due to alteration in different hormone expressions leading to genetic instability. Loss or gains of functions due to genetic instability were associated with the alterations in housekeeping genes. Up-regulation in c-myc, signal transducer and activator of transcription (STAT), CREB-regulated transcription coactivator (CRTC), and eukaryotic translation initiation factor 4E (eIF4E) may cause the development of breast cancer. Peptide hormones are commonly following the phosphoinositide 3-kinases (PI3K) pathway for activation of cell cycle causing uncontrolled proliferation. Although steroid hormones are following the Ras/Raf/mitogen-activated protein kinase (MEK) pathway, their hyper-activation of these pathways causes extracellular-signal-regulated kinase (ERK) and MAPK activation, leading to carcinogenesis.

Alteration in cell cycle proteins, oncogenes, tumor suppressor genes, transcription and translation factors lead to breast cancer. Apoptosis plays a vital role in the elimination of abnormal cells but failure in any of these apoptotic pathways may cause tumorigenesis. Hence, a complex interplay of hormonal and genetic factors is required to maintain homeostasis in breast cells. Imbalance in homeostasis of these hormone and genes may lead to breast cancer.

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab. Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy's efficacy and safety. Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions. Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC.

Epidermal growth factor receptor inhibitors (EGFRIs) induced cutaneous toxicity is a common adverse event (AE), although it is not as severe as major cancers, we still need to pay enough attention to them. Therefore, it is necessary to evaluate the diversity of EGFRI class drugs. The objective of this study was to conduct a scientific and systematic investigation into the correlation between EGFRI and cutaneous toxicities. The data accessed from the FDA adverse event reporting system database (FAERS) encompass a time frame spanning from January 2013 to March 2023. By utilizing reporting odds ratios (RORs), information components (ICs), proportional reporting ratios (PRRs), and chi-squared (χ2), the relationship between drugs and adverse reactions was evaluated through disproportionality analysis. Within the FAERS database, a total of 29,559 skin adverse events were recorded. A robust indication of the correlation between EGFRI and elderly patients (≥65 years) was identified. Among EGFRIs, erlotinib accounted for the largest proportion of skin adverse events (39.72%). Rash, dry skin, and pruritus ranked top among all preferred terms, and signals such as rash, skin lesions, and acneiform dermatitis were detected in every single drug. Clinicians should guide patients customize the treatment plan for each patient.

EGFR tyrosine kinase inhibitors (TKI) should always be considered when treating advanced/metastatic non-small cell lung cancer (NSCLC) with atypical EGFR mutations. The first choice of TKI depends on the specific mutation(s) present and its effect on structure and function of the EGFR protein. Afatinib is the only EGFR TKI currently FDA approved for atypical EGFR mutations and has the strongest data to support its use in PACC mutations, a subgroup of atypical EGFR mutations which includes G719X and S7681. Dacomitinib may also be an option for these mutations given similar efficacy to afatinib. In contrast, for classical-like mutations such as L861Q, osimertinib should be considered the first choice given that their behavior mimics that of the classical mutations exon 19 deletion and L858R. Osimertinib should also be utilized in the setting of a concurrent T790M mutation. Superior CNS penetrance and well managed toxicity profile may also be reasons to consider osimertinib. Given that the choice of TKI may depend on the specific mutation, it is crucial that every patient diagnosed with NSCLC undergo comprehensive sequencing to identify these mutations.

Lung cancer is the second most fatal disease worldwide. In the last few years, radiomics is being explored to develop prediction models for various clinical endpoints in lung cancer. However, the robustness of radiomic features is under question and has been identified as one of the roadblocks in the implementation of a radiomic-based prediction model in the clinic. Many past studies have suggested identifying the robust radiomic feature to develop a prediction model. In our earlier study, we identified robust radiomic features for prediction model development. The objective of this study was to develop and validate the robust radiomic signatures for predicting 2-year overall survival in non-small cell lung cancer (NSCLC). This retrospective study included a cohort of 300 stage I-IV NSCLC patients. Institutional 200 patients' data were included for training and internal validation and 100 patients' data from The Cancer Image Archive (TCIA) open-source image repository for external validation. Radiomic features were extracted from the CT images of both cohorts. The feature selection was performed using hierarchical clustering, a Chi-squared test, and recursive feature elimination (RFE). In total, six prediction models were developed using random forest (RF-Model-O, RF-Model-B), gradient boosting (GB-Model-O, GB-Model-B), and support vector(SV-Model-O, SV-Model-B) classifiers to predict 2-year overall survival (OS) on original data as well as balanced data. Model validation was performed using 10-fold cross-validation, internal validation, and external validation. Using a multistep feature selection method, the overall top 10 features were chosen. On internal validation, the two random forest models (RF-Model-O, RF-Model-B) displayed the highest accuracy; their scores on the original and balanced datasets were 0.81 and 0.77 respectively. During external validation, both the random forest models' accuracy was 0.68. In our study, robust radiomic features showed promising predictive performance to predict 2-year overall survival in NSCLC.

Human epidermal growth factor receptor 3 (HER3) is the only family member of the EGRF/HER family of receptor tyrosine kinases that lacks an active kinase domain (KD), which makes it an obligate binding partner with other receptors for its oncogenic role. When HER3 is activated in a ligand-dependent (NRG1/HRG) or independent manner, it can bind to other receptors (the most potent binding partner is HER2) to regulate many biological functions (growth, survival, nutrient sensing, metabolic regulation, etc.) through the PI3K-AKT-mTOR pathway. HER3 has been found to promote tumorigenesis, tumor growth, and drug resistance in different cancer types, especially breast and non-small cell lung cancer. Given its ubiquitous expression across different solid tumors and role in oncogenesis and drug resistance, there has been a long effort to target HER3. As HER3 cannot be targeted through its KD with small-molecule kinase inhibitors via the conventional method, pharmaceutical companies have used various other approaches, including blocking either the ligand-binding domain or extracellular domain for dimerization with other receptors. The development of treatment options with anti-HER3 monoclonal antibodies, bispecific antibodies, and different combination therapies showed limited clinical efficiency for various reasons. Recent reports showed that the extracellular domain of HER3 is not required for its binding with other receptors, which raises doubt about the efforts and applicability of the development of the HER3-antibodies for treatment. Whereas HER3-directed antibody-drug conjugates showed potentiality for treatment, these drugs are still under clinical trial. The currently understood model for dimerization-induced signaling remains incomplete due to the absence of the crystal structure of HER3 signaling complexes, and many lines of evidence suggest that HER family signaling involves more than the interaction of two members. This review article will significantly expand our knowledge of HER3 signaling and shed light on developing a new generation of drugs that have fewer side effects than the current treatment regimen for these patients.

Head and neck squamous cell carcinoma (HNSCC) contribute to a significant global cancer burden. Developments in current therapeutic approaches have improved patient outcomes but have limited efficacy in patients with unresectable and/or recurrent HNSCC. RM-1929 near-infrared photoimmunotherapy (NIR-PIT) is an emerging treatment that is currently being investigated in a Phase III clinical trial and has been conditionally approved for the treatment of unresectable and/or recurrent HNSCC in Japan. Here, we collect a series of case reports and clinical trial data to assess the efficacy of RM-1929 NIR-PIT. Disease control rates ranged from 66.7 to 100% across these studies, and overall response rates ranged from 43.3 to 100%, suggesting positive clinical outcomes. Low-grade postoperative localized pain and edema were the most frequently reported side effects, and preliminary reports on quality of life and pain levels suggest that RM-1929 NIR-PIT does not significantly decrease quality of life and is manageable with existing pain management strategies, including opioids. These preliminary data in real-world use of RM-1929 NIR-PIT show that it is a well-tolerated therapy that has clinically meaningful outcomes for patients with unresectable and/or recurrent HNSCC.

Targeted cancer treatments-designed to interfere with specific molecular signals responsible for tumor survival and progression-have shown benefit over conventional chemotherapies but may lead to diverse cutaneous adverse effects. This review highlights clinically significant dermatologic toxicities and their associated histopathologic findings, resulting from various targeted cancer drugs. Case reports and series, clinical trials, reviews, and meta-analyses are included for analysis and summarized herein. Cutaneous side effects resulting from targeted cancer therapies were reported with incidences as high as 90% for certain medications, and reactions are often predictable based on mechanism(s) of action of a given drug. Common and important reaction patterns included: acneiform eruptions, neutrophilic dermatoses, hand-foot skin reaction, secondary cutaneous malignancies, and alopecia. Clinical and histopathologic recognition of these toxicities remains impactful for patient care.

Virtual screening (VS) is a routine method to evaluate chemical libraries for lead identification. Therefore, the selection of appropriate protein structures for VS is an essential prerequisite to identify true actives during docking. But the presence of several crystal structures of the same protein makes it difficult to select one or few structures rationally for screening. Therefore, a computational prioritization protocol has been developed for shortlisting crystal structures that identify true active molecules with better efficiency. As identification of small-molecule inhibitors is an important clinical requirement for the T790M/L858R (TMLR) EGFR mutant, it has been selected as a case study. The approach involves cross-docking of 21 co-crystal ligands with all the structures of the same protein to select structures that dock non-native ligands with lower RMSD. The cross docking performance was then correlated with ligand similarity and binding-site conformational similarity. Eventually, structures were shortlisted by integrating cross-docking performance, and ligand and binding-site similarity. Thereafter, binding pose metadynamics was employed to identify structures having stable co-crystal ligands in their respective binding pockets. Finally, different enrichment metrics like BEDROC, RIE, AUAC, and EF1% were evaluated leading to the identification of five TMLR structures (5HCX, 5CAN, 5CAP, 5CAS, and 5CAO). These structures docked a number of non-native ligands with low RMSD, contain structurally dissimilar ligands, have conformationally dissimilar binding sites, harbor stable co-crystal ligands, and also identify true actives early. The present approach can be implemented for shortlisting protein targets of any other important therapeutic kinases.

To use population physiologically based pharmacokinetic (PopPBPK) modelling to optimize target expression, kinetics and clearance of HER1/2 directed therapeutic monoclonal antibodies (mAbs). Thus, to propose a general workflow of PopPBPK modelling and its application in clinical pharmacology.

Full PBPK model of pertuzumab (PTZ) was developed in patient population using Simcyp V21R1 incorporating mechanistic targeted-mediated drug disposition process by fitting known clinical PK and sparse receptor proteomics data to optimize target expression and kinetics of HER2 receptor. Trastuzumab (TTZ) PBPK modelling was used to validate the optimized HER2 target. Additionally, the simulator was also used to develop a full PBPK model for the HER1-directed mAb cetuximab (CTX) to assess the underlying targeted-mediated drug disposition-independent elimination mechanisms.

HER2 final parameterisation coming from the PBPK modelling of PTZ was successfully cross validated through PBPK modelling of TTZ with average fold error (AFE), absolute AFE and percent prediction error values for area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax ) of 1.13, 1.16 and 16, and 1.01, 1.07 and 7, respectively. CTX PBPK model performance was validated after the incorporation of an additional systemic clearance of 0.033 L/h as AFE and absolute AFE showed an acceptable predictive power of AUC and Cmax with percent prediction error of 13% for AUC and 10% for Cmax .

Optimisation of both system and drug related parameters were performed through PBPK modelling to improve model performance of therapeutic mAbs (PTZ, TTZ and CTX). General workflow was proposed to develop and apply PopPBPK to support clinical development of mAbs targeting same receptor.

Head and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer and account for 931,922 new cases and 467,125 deaths worldwide. About 90% of these cancers are of squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco and alcohol consumption and infection with oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making is becoming common practice in modern oncology, but in the management of patients with HNSCC, cytopathology or histopathology of tumour tissue remains the mainstream for diagnosis and treatment planning. Due to tumour heterogeneity and the lack of access to tumour due to its anatomical location, alternative methods to evaluate tumour activities are urgently needed. Liquid biopsy approaches can overcome issues such as tumour heterogeneity, which is associated with the analysis of small tissue biopsy. In addition, liquid biopsy offers repeat biopsy sampling, even for patients with tumours with access limitations. Liquid biopsy refers to biomarkers found in body fluids, traditionally blood, that can be sampled to provide clinically valuable information on both the patient and their underlying malignancy. To date, the majority of liquid biopsy research has focused on blood-based biomarkers, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and circulating microRNA. In this review, we will focus on ctDNA as a biomarker in HNSCC because of its robustness, its presence in many body fluids, adaptability to existing clinical laboratory-based technology platforms, and ease of collection and transportation. We will discuss mechanisms of ctDNA release into circulation, technological advances in the analysis of ctDNA, ctDNA as a biomarker in HNSCC management, and some of the challenges associated with translating ctDNA into clinical and future perspectives. ctDNA provides a minimally invasive method for HNSCC prognosis and disease surveillance and will pave the way in the future for personalized medicine, thereby significantly improving outcomes and reducing healthcare costs.

The diagnosis and treatment of medication-associated alopecia often challenges patients and physicians. While numerous studies on the topic exist, limited information on the strength and magnitude of these studies exists.

We investigated the most commonly prescribed medications with high levels of evidence to support associations with alopecia.

A list of most commonly prescribed medications was compiled using the "Top 100 Prescriptions, Sales" (Intercontinental Marketing Services) and "Top 200 Names Searched" (RxList.com). PubMed, Embase, and Web of Science were searched for "generic drug name" AND "alopecia" and "generic drug name" AND "hair loss." Two reviewers independently reviewed articles for drug, study type and level of evidence, and number of alopecia cases.

A total of 192 unique drugs were investigated, with 110 yielding positive search results. Of these, 13 were associated with alopecia in studies with strong levels of evidence (adalimumab, infliximab, budesonide, interferon β-1α, tacrolimus, enoxaparin, zoster vaccine, lamotrigine, docetaxel, capecitabine, erlotinib, imatinib, and bortezomib).

Only full-length articles available in the English language were included. The methodology used relied on lists of drugs based on their sales rather than number of prescriptions, which likely overrepresented expensive drugs.

Few studies with high levels of evidence have been conducted on the topic of medication-associated alopecia. The mechanisms of hair loss must be further identified to provide effective management.

Current clinical and observational evidence supports the EXTREME regimen as one of the standards of care for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) followed by the administration of immune checkpoint inhibitors (ICIs). In addition to the inhibition of the epidermal growth factor receptor (EGFR) pathway, cetuximab-mediated EGFR blockade has been shown to modulate tumor microenvironment (TME) characteristics, such as antibody-dependent cellular cytotoxicity (ADCC) activity, cytotoxic T-lymphocyte (CTL) infiltration into the tumor, anti-angiogenesis activity, and cytokine secretion via associated natural killer (NK) cells, etc.. On the other hand, there are reports that nivolumab affects the TME via Programmed cell death 1 (PD-1) inhibition, Interleukin-10 upregulation via T-cells, myeloid-derived suppressor cell-mediated immune escape induction, and tumor vessel perfusion by promoting CD8 + T-cell accumulation and Interferon-γ production in treatment-sensitive tumor cells. Actually, nivolumab administration can give T cells in the TME both immune superiority and inferiority. HNSCC treatment using cetuximab increases the frequency of FoxP3 + intratumoral effector regulatory T cells (Tregs) expressing CTL associated antigen (CTLA)-4, and targeting CTLA-4 + Tregs using ipilimumab restores the cytolytic function of NK cells, which mediate ADCC activity. Treg-mediated immune suppression also contributes to clinical response to cetuximab treatment, suggesting the possibility of the addition of ipilimumab or the use of other Treg ablation strategies to promote antitumor immunity. Moreover, also in hyper progression disease (HPD), intratumoral frequency of FoxP3 + effector Tregs expressing CTLA-4 is increased. Therefore, combination treatment with cetuximab plus anti-CTLA-4 antibody ipilimumab for HNSCC and this combination therapy after nivolumab administration for HPD may be expected to result in a higher tumor-control response. Based on the above evidence, we here suggest the efficacy of using these therapeutic strategies for patients with local-advanced, recurrent, and metastatic HNSCC and patients who do not respond well to nivolumab administration.

Squamous cell carcinoma (SCC) is a relatively common and heterogenous malignancy of different organs, such as the skin, esophagus, and lungs. Although most cases experience good survival with surgical methods, management of advanced types of the disease remains challenging. Several modalities, including different chemotherapy regimens and immunotherapies, have been investigated in this matter, among which Monoclonal antibodies (Mabs) are one of the most promising ones. Since the development of Mabs, they have been widely used to treat different diseases. Mabs have shown significant efficacy with high specificity along with acceptable safety, which makes them a favorable option in cancer therapy. In this article, we aimed to review the different aspects of using Mabs in SCC therapy.

We found that treating with different Mabs has shown excellent efficacy accompanied by acceptable safety in treating SCC of different organs. Therefore, Mabs are considered great options in the treatment of SCC, especially in advanced cases. Overall, two highly potent types of Mabs in SCC therapy are anti-EGFR Mabs and checkpoint inhibitors, especially Cetuximab, Nimotuzumab, and PD-1 inhibitors. Bevacizumab is also a promising option as adjuvant therapy to other modalities.

Although some Mabs have shown promising outcomes in SCC therapy, their application as a part of cancer treatment depends on further investigations regarding cost-effectiveness and predictors of response. FDA has approved several Mabs in SCC therapies, and Mabs may have a crucial role in this era in the near future, especially in treating head and neck and esophageal SCC and metastatic lung cancer.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis.

This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed.

This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD.

This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.

In this study, we report a general approach to the design of a new generation of small-molecule sensors that produce a zero background but are brightly fluorescent in the near-IR spectral range upon selective interaction with a biomolecular target. We developed a fluorescence turn-on/-off mechanism based on the aggregation/deaggregation of phthalocyanine chromophores. As a proof of concept, we designed, prepared, and characterized sensors for in-cell visualization of epidermal growth factor receptor (EGFR) tyrosine kinase. We established a structure/bioavailability correlation, determined conditions for the optimal sensor uptake and imaging, and demonstrated binding specificity and applications over a wide range of treatment options involving live and fixed cells. The new approach enables high-contrast imaging and requires no in-cell chemical assembly or postexposure manipulations (i.e., washes). The general design principles demonstrated in this work can be extended toward sensors and imaging agents for other biomolecular targets.

The epidermal growth factor receptor (EGFR) has been shown to be extremely important in numerous signaling pathways, particularly those involved in cancer progression. Many therapeutic inhibitors, consisting of both small molecules and monoclonal antibodies, have been developed to target inflammatory, triple-negative and metastatic breast cancer. With the emergence of resistance in breast cancer treatment strategies, there is a need to develop novel drug targets that not only overcome resistance, but also exhibit low toxicity and high specificity. The work presented here focuses on the identification of new inhibitors against the EGFR protein using combined computational approaches. Using a comprehensive machine learning-based virtual screening approach complemented by other computational approaches, we identified six new molecules from the ZINC database. The gold docking score of these six novel molecules is 125.95, 125.38, 123.13, 119.71, 115.64 and 113.73, respectively, while the gold score of the control group is 120.74. In addition, we also analyzed the FEC value of these compounds and found that the values of compounds 1, 2, 3 and 4 (-61.82, -63.98, -67.98 and -63.32, respectively) were higher are than those of the control group (-61.05). Furthermore, these molecules showed highly stable RMSD plots and good interaction of hydrogen bonds. The identified inhibitors provided interesting insights for understanding the electronic, hydrophobic, steric and structural requirements for EGFR inhibitory activity. Distinguishing these novel molecules could lead to the development of new drugs useful in treating breast cancer.Communicated by Ramaswamy H. Sarma.

Radiotherapy is the major treatment of non-small cell lung cancer (NSCLC). The radioresistance and toxicity are the main obstacles that leading to therapeutic failure and poor prognosis. Oncogenic mutation, cancer stem cells (CSCs), tumor hypoxia, DNA damage repair, epithelial-mesenchymal transition (EMT), and tumor microenvironment (TME) may dominate the occurrence of radioresistance at different stages of radiotherapy. Chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors are combined with radiotherapy to treat NSCLC to improve the efficacy. This article reviews the potential mechanism of radioresistance in NSCLC, and discusses the current drug research to overcome radioresistance and the advantages of Traditional Chinese medicine (TCM) in improving the efficacy and reducing the toxicity of radiotherapy.

The time interval between the diagnosis of tumor in a patient and the initiation of treatment plays a key role in determining the survival rates. Consequently, theranostics, which is a combination of diagnosis and treatment, can be expected to improve survival rates. Early detection and immediate treatment initiation are particularly important in the management of melanoma, where survival rates decrease considerably after metastasis. The present work reports for the first time the application of fluorescein isothiocyanate (FITC)-tagged epidermal growth factor receptor (EGFR)-functionalized ceria nanoparticles, which exhibit intrinsic reactive oxygen species (ROS)-mediated anticancer effects, for the EGFR-targeted diagnosis and treatment of melanoma. The theranostic activity was demonstrated using two-dimensional (2D) and three-dimensional (3D) models of parental and metastatic melanoma. Confocal imaging studies confirm the diagnostic activity of the system. The therapeutic efficiency was evaluated using cell viability studies and ROS measurements. The ROS elevation levels are compared across the 2D and 3D models. Significant enhancement in the generation of cellular ROS and absence in mitochondrial ROS are observed in the 2D models. In contrast, significant elevations in both ROS types are observed for the 3D models, which are significantly higher for the metastatic spheroids than the parental spheroids, thus indicating the suitability of this nanoformulation for the treatment of metastatic melanoma.

An increasing number of immunomodulators, either anti-inflammatory or immunity-enhancing, have brought about a revolutionary effect in the management of a variety of autoimmune disorders and malignancies. However, their ability to cause gastrointestinal (GI) injury and induce GI symptoms has been increasingly and unexpectedly recognized. GI injury associated with immunomodulators may demonstrate various histologic and endoscopic patterns. Optimal diagnosis and treatment require a multidisciplinary approach. This review aims to provide an overview of the literature on its pathogenesis, the clinical, endoscopic, and histologic features, and suggested approaches to manage these newly recognized immunomodulator-induced GI adverse effects (AEs). We also reviewed current biomarkers predictive of GI toxicity and potential risk factors to identify susceptible patients. In addition, these immune-mediated AEs were compared with inflammatory bowel disease, a well-documented form of inflammation-driven GI injury. We hope this review will raise awareness and vigilance among clinicians of these entities to increase early diagnosis and rapid referral to specialist care.

Cancer is a major cause of human death all over the world. Traditional cancer treatments include surgery, radiotherapy, chemotherapy, immunotherapy, and hormone therapy. Although these conventional treatment methods improve the overall survival rate, there are some problems, such as easy recurrence, poor treatment, and great side effects. Targeted therapy of tumors is a hot research topic at present. Nanomaterials are essential carriers of targeted drug delivery, and nucleic acid aptamers have become one of the most important targets for targeted tumor therapy because of their high stability, high affinity, and high selectivity. At present, aptamer-functionalized nanomaterials (AFNs), which combine the unique selective recognition characteristics of aptamers with the high-loading performance of nanomaterials, have been widely studied in the field of targeted tumor therapy. Based on the reported application of AFNs in the biomedical field, we introduce the characteristics of aptamer and nanomaterials, and the advantages of AFNs first. Then introduce the conventional treatment methods for glioma, oral cancer, lung cancer, breast cancer, liver cancer, colon cancer, pancreatic cancer, ovarian cancer, and prostate cancer, and the application of AFNs in targeted therapy of these tumors. Finally, we discuss the progress and challenges of AFNs in this field.