|
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 |
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 |
AlteredExpression
|
disease |
BEFREE |
Taken together, the findings of this study suggest that the protein levels of HIF2A and VEGFA in tumor tissue may serve as independent prognostic factors in ccRCC. ccRCC patients with increased intratumoral HIF2A and VEGFA protein levels, and unaltered VHL protein levels, are not likely to benefit from sunitinib treatment following nephrectomy; however, this hypothesis requires verification by large‑scale replication studies.
|
31268155 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
We demonstrated that ccRCC patients with HIF-2α<sup>high</sup> tumors exhibited reduced overall survival (p = 0.025) and recurrence-free survival (p < 0.001).
|
30758643 |
2019 |
|
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 |
Biomarker
|
disease |
BEFREE |
In this review, we briefly discuss the role of HIF-2α in ccRCC and provide insight into recent advances in the discovery, development, and mode of action of HIF-2α allosteric inhibitors.
|
31541711 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Everolimus resistance in clear cell renal cell carcinoma: miRNA-101 and HIF-2α as molecular triggers?
|
31267758 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
The drug blocks the HIF2α transcription factor and is being tested in a phase I/II trial for clear cell renal cell carcinoma.
|
31186237 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Future study is warranted to determine if iron deprivation using chelator drugs provides an effective therapeutic strategy for targeting HIF-2α and suppressing tumor progression in ccRCC patients.
|
30553971 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
These findings support testing CDK4/6 inhibitors as treatments for ccRCC, alone and in combination with HIF-2α inhibitors.
|
31575731 |
2019 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Our first HIF-2α inhibitor PT2385 demonstrated promising proof of concept clinical activity in heavily pretreated advanced ccRCC patients.
|
31282155 |
2019 |
|
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 |
AlteredExpression
|
disease |
BEFREE |
Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC.
|
30144808 |
2018 |
|
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 |
AlteredExpression
|
disease |
BEFREE |
Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038).
|
29357946 |
2018 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
VHL is a major tumour suppressor in ccRCC and loss of VHL leads to stabilisation of hypoxia inducible factors HIF-1α and HIF-2α.
|
29872221 |
2018 |
|
Conventional (Clear Cell) Renal Cell Carcinoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice.
|
29033582 |
2017 |
|
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 |
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 |
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 |
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 |
Biomarker
|
disease |
BEFREE |
We found that the anti-angiogenic TKI sunitinib disrupted the balance between HIF-1α and HIF-2α in RCCs and led to a protective effect on HUVECs against sunitinib treatment when cultured with conditioned medium.
|
28572533 |
2017 |
|
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 |