Biomarkers Towards New Era of Therapeutics for Metastatic Renal Cell Carcinoma

Abstract

With the improved knowledge of molecular oncology and the introduction of targeted therapies as well as immunotherapies, there has been significant progress in the treatment of patients with metastatic renal cell carcinoma (mRCC). At present, treatment decisions are still made mainly based on clinical factors because no validated prognostic and predictive biomarkers for mRCC exist. Currently, inflammatory markers, genetic markers, and immune checkpoint molecules are candidate biomarkers for more personalized treatment of mRCC. RCC has been considered to be an inflammatory tumor and its underlying inflammatory mechanism would play some roles in forming resistance to systemic therapy. The von Hippel-Lindau (VHL) gene is inactivated by either mutation or methylation in over 80% of clear cell RCC (ccRCC). Thus, most, if not all, ccRCC may have deregulation of the VHL pathway. For some reason, VHL status is difficult to use as a prognostic marker. Polybromo 1 (PBRM1) is the second most frequently mutated gene in ccRCC and loss of function mutations in the PBRM1 gene have been shown to be associated with improved survival in patients with mRCC treated with systemic therapies. The expression of programmed death ligand 1 (PD-L1) on tumor cells in RCC seems to be associated with a higher tumor stage, a worse response to tyrosine kinase inhibitor (TKI) therapy, and a worse prognosis. Future challenges are required to develop and validate predictive biomarkers in order to establish a more personalized treatment for mRCC.