On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models

Hyejin Cho, Xinlin Du, James P. Rizzi, Ella Liberzon, Abhishek A. Chakraborty, Wenhua Gao, Ingrid Carvo, Sabina Signoretti, Richard K. Bruick, John A. Josey, Eli M. Wallace, William G. Kaelin

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.

Original languageEnglish (US)
Pages (from-to)107-111
Number of pages5
JournalNature
Volume539
Issue number7627
DOIs
StatePublished - 2016

Fingerprint

Kidney Neoplasms
Renal Cell Carcinoma
Tumor Suppressor Proteins
Transcription Factors
Biomarkers
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Cho, H., Du, X., Rizzi, J. P., Liberzon, E., Chakraborty, A. A., Gao, W., ... Kaelin, W. G. (2016). On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature, 539(7627), 107-111. https://doi.org/10.1038/nature19795

On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. / Cho, Hyejin; Du, Xinlin; Rizzi, James P.; Liberzon, Ella; Chakraborty, Abhishek A.; Gao, Wenhua; Carvo, Ingrid; Signoretti, Sabina; Bruick, Richard K.; Josey, John A.; Wallace, Eli M.; Kaelin, William G.

In: Nature, Vol. 539, No. 7627, 2016, p. 107-111.

Research output: Contribution to journalArticle

Cho, H, Du, X, Rizzi, JP, Liberzon, E, Chakraborty, AA, Gao, W, Carvo, I, Signoretti, S, Bruick, RK, Josey, JA, Wallace, EM & Kaelin, WG 2016, 'On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models', Nature, vol. 539, no. 7627, pp. 107-111. https://doi.org/10.1038/nature19795
Cho H, Du X, Rizzi JP, Liberzon E, Chakraborty AA, Gao W et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature. 2016;539(7627):107-111. https://doi.org/10.1038/nature19795
Cho, Hyejin ; Du, Xinlin ; Rizzi, James P. ; Liberzon, Ella ; Chakraborty, Abhishek A. ; Gao, Wenhua ; Carvo, Ingrid ; Signoretti, Sabina ; Bruick, Richard K. ; Josey, John A. ; Wallace, Eli M. ; Kaelin, William G. / On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. In: Nature. 2016 ; Vol. 539, No. 7627. pp. 107-111.
@article{57b81e46b61042aa933471f89b49ec69,
title = "On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models",
abstract = "Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.",
author = "Hyejin Cho and Xinlin Du and Rizzi, {James P.} and Ella Liberzon and Chakraborty, {Abhishek A.} and Wenhua Gao and Ingrid Carvo and Sabina Signoretti and Bruick, {Richard K.} and Josey, {John A.} and Wallace, {Eli M.} and Kaelin, {William G.}",
year = "2016",
doi = "10.1038/nature19795",
language = "English (US)",
volume = "539",
pages = "107--111",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7627",

}

TY - JOUR

T1 - On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models

AU - Cho, Hyejin

AU - Du, Xinlin

AU - Rizzi, James P.

AU - Liberzon, Ella

AU - Chakraborty, Abhishek A.

AU - Gao, Wenhua

AU - Carvo, Ingrid

AU - Signoretti, Sabina

AU - Bruick, Richard K.

AU - Josey, John A.

AU - Wallace, Eli M.

AU - Kaelin, William G.

PY - 2016

Y1 - 2016

N2 - Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.

AB - Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.

UR - http://www.scopus.com/inward/record.url?scp=84994626953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994626953&partnerID=8YFLogxK

U2 - 10.1038/nature19795

DO - 10.1038/nature19795

M3 - Article

VL - 539

SP - 107

EP - 111

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7627

ER -