Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Rohan Garje
ORCID logo ,
Josiah J. An
,
kevin Sanchez
,
Austin Greco
,
Jeffrey Stolwijk
,
Eric Devor
,
Youcef Rustum
,
Yousef Zakharia
*
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.

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.

Keywords

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

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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