PMID- 30513765
OWN - NLM
STAT- MEDLINE
DCOM- 20190325
LR  - 20200225
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 12
DP  - 2018 Dec 1
TI  - Current Landscape and the Potential Role of Hypoxia-Inducible Factors and 
      Selenium in Clear Cell Renal Cell Carcinoma Treatment.
LID - 10.3390/ijms19123834 [doi]
LID - 3834
AB  - 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.
FAU - Garje, Rohan
AU  - Garje R
AUID- ORCID: 0000-0002-7244-5602
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of Iowa, Iowa City, IA 52242, USA. josiah-an@uiowa.edu.
AD  - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA. 
      josiah-an@uiowa.edu.
FAU - An, Josiah J
AU  - An JJ
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of Iowa, Iowa City, IA 52242, USA. josiah-an@uiowa.edu.
FAU - Sanchez, Kevin
AU  - Sanchez K
AD  - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. 
      kevin-sanchez@uiowa.edu.
FAU - Greco, Austin
AU  - Greco A
AD  - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. 
      austin-greco@uiowa.edu.
FAU - Stolwijk, Jeffrey
AU  - Stolwijk J
AD  - 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.
FAU - Devor, Eric
AU  - Devor E
AD  - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, 
      USA. eric-devor@uiowa.edu.
FAU - Rustum, Youcef
AU  - Rustum Y
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of Iowa, Iowa City, IA 52242, USA. Youcef.Rustum@RoswellPark.org.
AD  - Roswell Park Cancer Institute, Buffalo, NY 14203, USA. 
      Youcef.Rustum@RoswellPark.org.
FAU - Zakharia, Yousef
AU  - Zakharia Y
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of Iowa, Iowa City, IA 52242, USA. yousef-zakharia@uiowa.edu.
AD  - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA. 
      yousef-zakharia@uiowa.edu.
LA  - eng
GR  - P30 CA086862/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20181201
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - H6241UJ22B (Selenium)
SB  - IM
MH  - Angiogenesis Inhibitors/pharmacology
MH  - Carcinogenesis/metabolism/pathology
MH  - Carcinoma, Renal Cell/*metabolism/pathology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Kidney Neoplasms/*metabolism/pathology
MH  - Selenium/*metabolism
PMC - PMC6321165
OTO - NOTNLM
OT  - PD-L1
OT  - VEGF
OT  - clear cell renal cell carcinoma
OT  - hypoxia-inducible factors (HIFs)
OT  - mTOR inhibitors
OT  - miRNA
OT  - selenium
COIS- The authors declare no conflict of interest.
EDAT- 2018/12/06 06:00
MHDA- 2019/03/26 06:00
PMCR- 2018/12/01
CRDT- 2018/12/06 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2018/11/27 00:00 [revised]
PHST- 2018/11/28 00:00 [accepted]
PHST- 2018/12/06 06:00 [entrez]
PHST- 2018/12/06 06:00 [pubmed]
PHST- 2019/03/26 06:00 [medline]
PHST- 2018/12/01 00:00 [pmc-release]
AID - ijms19123834 [pii]
AID - ijms-19-03834 [pii]
AID - 10.3390/ijms19123834 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Dec 1;19(12):3834. doi: 10.3390/ijms19123834.