Preprint Review Version 1 This version is not peer-reviewed

Current Landscape and the Potential Role of HIF and Selenium in Clear Cell Renal Cell Carcinoma Treatment

Version 1 : Received: 18 September 2018 / Approved: 19 September 2018 / Online: 19 September 2018 (05:10:22 CEST)

A peer-reviewed article of this Preprint also exists.

Garje, R.; An, J.J.; Sanchez, K.; Greco, A.; Stolwijk, J.; Devor, E.; Rustum, Y.; Zakharia, Y. Current Landscape and the Potential Role of Hypoxia-Inducible Factors and Selenium in Clear Cell Renal Cell Carcinoma Treatment. Int. J. Mol. Sci. 2018, 19, 3834. Garje, R.; An, J.J.; Sanchez, K.; Greco, A.; Stolwijk, J.; Devor, E.; Rustum, Y.; Zakharia, Y. Current Landscape and the Potential Role of Hypoxia-Inducible Factors and Selenium in Clear Cell Renal Cell Carcinoma Treatment. Int. J. Mol. Sci. 2018, 19, 3834.

Journal reference: Int. J. Mol. Sci. 2018, 19, 3834
DOI: 10.3390/ijms19123834

Abstract

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

Subject Areas

clear cell renal cell carcinoma; hypoxia inducible factors (HIFs); selenium; PD-L1; miRNA; VEGF; mTOR inhibitors

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