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Int J Mol Sci. 2018 Dec 1;19(12). pii: E3834. doi: 10.3390/ijms19123834.

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

Author information

1
Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, Iowa City, IA 52242, USA. josiah-an@uiowa.edu.
2
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA. josiah-an@uiowa.edu.
3
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. kevin-sanchez@uiowa.edu.
4
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. austin-greco@uiowa.edu.
5
Interdisciplinary Graduate Program in Human Toxicology, Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA. jeffrey-stolwijk@uiowa.edu.
6
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA. eric-devor@uiowa.edu.
7
Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, Iowa City, IA 52242, USA. Youcef.Rustum@RoswellPark.org.
8
Roswell Park Cancer Institute, Buffalo, NY 14203, USA. Youcef.Rustum@RoswellPark.org.
9
Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, Iowa City, IA 52242, USA. yousef-zakharia@uiowa.edu.
10
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA. yousef-zakharia@uiowa.edu.

Abstract

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.

KEYWORDS:

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

PMID:
30513765
PMCID:
PMC6321165
DOI:
10.3390/ijms19123834
[Indexed for MEDLINE]
Free PMC Article

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