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

Abstract

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.

Keywords: A-674563 (PubChem CID: 11314340); Biomarkers; Dovitinib (PubChem CID: 135398510); Hymecromone (PubChem CID: 5280567); Molecular mechanisms; NVP-BEZ235 (PubChem CID: 11977753); Niclosamide (PubChem CID: 4477); Nutlin-3 (PubChem CID: 216345); Paclitaxel (PubChem CID: 36314); Pazopanib (PubChem CID: 10113978); Precision therapy; Renal cell carcinoma; Selumetinib (PubChem CID: 10127622); Sorafenib (PubChem CID: 216239); Sorafenib resistance; Sunitinib (PubChem CID: 5329102); TH-302 (PubChem CID: 11984561); Temsirolimus (PubChem CID: 6918289); Trametinib (PubChem CID: 11707110); Ubenimex (PubChem CID: 72172).