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

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145 Scopus citations

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

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ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Cho, H., Du, X., Rizzi, J. P., Liberzon, E., Chakraborty, A. A., Gao, W., Carvo, I., Signoretti, S., Bruick, R. K., Josey, J. A., Wallace, E. M., & 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