Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Purpose: Apatinib resistance is the main obstacle to the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate the function of Erb-B2 receptor tyrosine kinase 2 (ERBB2) and stimulator of interferon response cGAMP interactor (STING) in apatinib resistance in HNSCC.
Method: The Cancer Genome Atlas database of HNSCC was used to analyze the relationship between vascular endothelial growth factor receptor 2 (VEGFR2) expression and prognosis. An apatinib resistant (AR) HNSCC cell line was constructed based on the CAL27 cell line. RNA sequencing was performed to explore the differentially expressed mRNAs. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were used to evaluate the expression and phosphorylation level VEGFR2, ERBB2, STING, and related proteins. Apatinib resistance was evaluated by colony formation and cell viability assays. A mouse subcutaneous tumor formation model was established to evaluate the efficiency of combination treatment and vascularization was evaluated by assessing CD31 immunofluorescence.
Result: The expression of VEGFR2 was high in tumor of patients with HNSCC. Western blotting and qRT-PCR revealed that in AR cells, ERBB2 expression was high, whereas the expression of STING was low. Targeted treatment of ERBB2 using lapatinib could attenuate apatinib resistance. Further research confirmed that overexpressing could decrease ERBB2 expression.
Conclusion: STING could sensitize AR cells to apatinib by decreasing ERBB2 expression. The combination of lapatinib or a STING agonist with apatinib ameliorated acquired apatinib resistance in a synergistic manner.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436913 | PMC |
| http://dx.doi.org/10.18632/aging.203475 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The tumor suppressor DACT3 sensitizes triple-negative breast cancer to apatinib by inhibiting the Wnt/β-catenin pathway.
Transl Oncol
August 2025
Department of Breast Center, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing University Cancer Hospital, Chongqing 400030, China. Electronic address:
Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), shows efficient antitumor activity in heavily pretreated metastatic triple-negative breast cancer (TNBC). However, not all patients respond to apatinib, indicating that it is necessary to identify response biomarkers for more precise treatment and investigate the underlying mechanisms of apatinib resistance to develop new treatment strategies for TNBC. In this study, we identified the disheveled binding antagonist of beta-catenin 3 (DACT3) as a biomarker for apatinib sensitivity, as its expression level is significantly higher in apatinib-sensitive patients and positively correlates with longer survival.
View Article and Find Full Text PDFTargeting tumor vascular endothelial cells for hepatocellular carcinoma treatment.
World J Gastroenterol
August 2025
Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT 06030, United States.
Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide. The predominant type of primary liver cancer is hepatocellular carcinoma (HCC). Tumor vascular endothelial cells (VECs), a major component of cells in the microenvironment of HCC, play multifaceted roles in contributing to tumor angiogenesis, proliferation, and migration, as well as therapeutic resistance by attracting myeloid-derived suppressor cells and suppressing cytotoxic CD8 T cell differentiation and function.
View Article and Find Full Text PDFCholesterol confers resistance to Apatinib-mediated ferroptosis in gastric cancer.
Cell Biosci
July 2025
Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
Background: Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. Apatinib is a third-line treatment for gastric cancer. However, the development of resistance significantly limits its efficacy, and effective and safe strategies to overcome Apatinib resistance remain elusive.
View Article and Find Full Text PDFApatinib modulates sorafenib-resistant hepatocellular carcinoma through inhibiting the EGFR/JNK/ERK signaling pathway.
Oncol Res
June 2025
Liver Gall Bladder and Pancreatic Surgery Ward, Qinghai Red Cross Hospital, Xining, 810001, China.
Objectives: Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma (HCC) patients. However, the underlying mechanism remains ambiguous. The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both and .
View Article and Find Full Text PDFClinical study of adebrelimab in combination with apatinib and irinotecan for PD-1 inhibitor-ineffective advanced-stage gastric cancer: study protocol for a single-arm, single-centre, exploratory trial.
BMJ Open
June 2025
Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
Introduction: Immunotherapy has revolutionised cancer treatment. Immune checkpoint inhibitors have demonstrated significant efficacy across multiple tumour types, including gastric cancer, where several approved programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors show promising antitumour activity. While PD-L1 expression serves as a predictive biomarker for PD-1 inhibitor response, and PD-L1-positive patients generally show better outcomes, therapeutic resistance remains a challenge.
View Article and Find Full Text PDF