4.7 Review

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

Journal

PHARMACOLOGICAL RESEARCH
Volume 170, Issue -, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105732

Keywords

Renal cell carcinoma; Sorafenib resistance; Molecular mechanisms; Biomarkers; Precision therapy

Funding

  1. International Cooperation Program of National Natural Science Foundation of China [31961143005]
  2. Chengdu Science and Technology Program [2017GH02-00062-HZ, 2020-GH02-00056-HZ]

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Sorafenib is an effective drug for RCC treatment, but only a small number of patients benefit from it, and sorafenib resistance is increasing. The molecular mechanisms of sorafenib resistance in RCC are not completely understood at present.
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.

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