New frontiers against sorafenib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers

• Published in: Pharmacological research 2021-08, Vol.170, p.105732-105732, Article 105732
• Main Authors: He, Yu, Luo, Yang, Huang, Lan, Zhang, Dan, Wang, Xixi, Ji, Jiayi, Liang, Shufang
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - secondary; Clinical Decision-Making; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Genomics; Humans; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Molecular mechanisms; Precision therapy; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Renal cell carcinoma; Signal Transduction; Sorafenib - adverse effects; Sorafenib - pharmacokinetics; Sorafenib - therapeutic use; Sorafenib resistance; Treatment Outcome
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2021.105732

Renal cell carcinoma (RCC) is a highly vascularized tumor and prone to distant metastasis. Sorafenib is the first targeted multikinase inhibitor and first-line chemical drug approved for RCC therapy. In fact, only a small number of RCC patients benefit significantly from sorafenib treatment, while the growing prevalence of sorafenib resistance has become a major obstacle for drug therapy effectivity of sorafenib. The molecular mechanisms of sorafenib resistance in RCC are not completely understood by now. Herein, we comprehensively summarize the underlying mechanisms of sorafenib resistance and molecular biomarkers for predicting sorafenib responsiveness. Moreover, we outline strategies suitable for overcoming sorafenib resistance and prospect potential approaches for identifying biomarkers associated with sorafenib resistance in RCC, which contributes to guide individualized and precision drug therapy. [Display omitted] •Most RCC patients do not respond well to sorafenib treatment due to sorafenib resistance.•Sorafenib resistance includes several interplaying ways of biological molecules, signaling pathways and pharmacokinetics.•Sorafenib resistance biomarkers are useful for predicting sorafenib responsiveness.•Combination therapy, sequential therapy with sorafenib and other drugs are available for overcoming sorafenib resistance.•Better understanding of sorafenib resistance guides rational use of sorafenib for RCC therapy.