Current Landscape and the Potential Role of Hypoxia-Inducible Factors and Selenium in Clear Cell Renal Cell Carcinoma Treatment.

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) has led to the development of biologically-driven targeted therapies. Hypoxia-inducible factors (HIFs), angiogenic growth factors, von Hippel⁻Lindau (VHL) gene mutations, and oncogenic microRNAs (miRNAs) play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of vascular endothelial growth factor (VEGF) inhibitors, Mechanistic target of rapamycin (mTOR) inhibitors, and immunotherapeutic agents, which have significantly improved the 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, selenium, and agents like 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 clear cell RCC (ccRCC) tumors.

International journal of molecular sciences. 2018 Dec 01*** epublish ***

Rohan Garje, Josiah J An, Kevin Sanchez, Austin Greco, Jeffrey Stolwijk, Eric Devor, Youcef Rustum, Yousef Zakharia

Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, Iowa City, IA 52242, USA. ., Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. ., Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. ., Interdisciplinary Graduate Program in Human Toxicology, Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA. ., Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA. ., Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, Iowa City, IA 52242, USA. ., Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, Iowa City, IA 52242, USA. .