|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Two recent independent studies published in <i>Nature</i> show robust responses of clear cell renal cell carcinoma (ccRCC) cell lines, preclinical ccRCC xenograft models and, remarkably, a patient with progressive ccRCC despite receiving multiple lines of treatment, to the long-awaited, recently developed inhibitors of hypoxia-inducible factor 2-alpha (HIF2α).
|
28667082 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
HIF2A germline-mutation-induced polycythemia in a patient with VHL-associated renal-cell carcinoma.
|
29172931 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for Renal Cell Carcinoma.
|
28951458 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1.
|
22113997 |
2012 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
A subset of clear cell renal cell carcinoma (ccRCC) tumors exhibit a HIF1A gene mutation, yielding two ccRCC tumor types, H1H2 type expressing both HIF1α and HIF2α, and H2 type expressing HIF2α, but not functional HIF1α protein.
|
28092369 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1).
|
31231134 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC.
|
21131975 |
2011 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
The authors observed evidence of interactions between PhIP and RCC susceptibility variants in 2 genes: inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (rs718314; multiplicative P for interaction = .03 and additive P for interaction =.002) and endothelial PAS domain-containing protein 1 (EPAS1) (rs7579899; additive P for interaction =.06).
|
26551148 |
2016 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
CTD_human |
Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC.
|
21131975 |
2011 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
We demonstrate that functional delivery of a HIF2α-specific RNAi trigger resulted in HIF2α gene silencing and subsequent tumor growth inhibition and degeneration in an established orthotopic ccRCC xenograft model.<i></i>.
|
29079709 |
2018 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
In kidney cancer, HIF-2α is believed to be the most important driver for development and progression of clear cell renal cell carcinoma (ccRCC), highlighting the therapeutic potential of HIF-2 antagonists in this disease.
|
28217462 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
The hypoxia-inducible factors HIF1α and HIF2α play a crucial role in ccRCC initiation and progression.
|
27507852 |
2016 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
EPAS1 was detected in all of the RCC cell lines examined.
|
11301389 |
2001 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Mutation analysis of hypoxia-inducible factors HIF1A and HIF2A in renal cell carcinoma.
|
20032376 |
2009 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Our findings also suggest that MTHFD2 and HIF-2α form a positive feedforward loop in RCC, promoting metabolic reprograming and tumor growth.
|
31289360 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
We demonstrate that HIF2α promotes lipid storage, ER homeostasis, and cell viability in ccRCC via upregulation of the LD coat protein PLIN2, revealing a novel function for the well-documented "clear-cell" phenotype and identifying ER stress as a targetable vulnerability created by HIF2α/PLIN2 suppression in this common renal malignancy.
|
25829424 |
2015 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate ( S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1 H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385).
|
30289716 |
2018 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Herein, we provide mechanistic evidence that HIF-2α can be degraded in cytoplasm under hypoxic conditions via the 26S proteasome and that MDM2 is the E3 ligase which induces the hypoxic degradation of HIF-2α in PI-3K-dependent manner in VHL-deficient RCC cells.
|
25578041 |
2015 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients.
|
23378636 |
2013 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
These studies validate HIF2α as a therapeutic target in ccRCC, reveal variable sensitivity to HIF2α antagonism, and provide the foundation for predictive biomarker-driven clinical trials.
|
27728802 |
2016 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Hypoxia-inducible factor 2alpha (HIF-2α) antagonists -PT2385, and PT2399 have been shown to have promising results in the management of clear cell renal cell carcinoma by targeting the HIF-2α pathway in recent and ongoing clinical trials (PT2799).
|
28946040 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Herein, we summarize the molecular background behind the use of HIF-2α inhibitors in ccRCC and give an overview of the development of new agents in this setting.
|
28259286 |
2017 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
HIF2α is involved in the expansion of CXCR4-positive cancer stem-like cells in renal cell carcinoma.
|
26439684 |
2015 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
A small molecule inhibitor that binds to HIF-2α and blocks dimerization with HIF-1β is in clinical trials for the treatment of renal cell carcinoma.
|
30625281 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used.
|
23506478 |
2013 |