HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor, in Patients with Clear Cell Renal Cell Carcinoma.
Kevin Dale CourtneyYuanqing MaAlberto Diaz de LeonAlana ChristieZhiqun XieLayton WoolfordNirmish SinglaAllison JoyceHaley HillAnanth J MadhuranthakamQing YuanYin XiYue ZhangJenny ChangOluwatomilade FatundeYull ArriagaArthur E FrankelSanjeeva KalvaSong ZhangTiffani McKenzieOscar Reig TorrasRobert A FiglinBrian I RiniRenée M McKayPayal KapurTao WangIvan PedrosaJames BrugarolasPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2019)
These findings demonstrate a core dependency on HIF-2 in metastatic ccRCC and establish PT2385 as a highly specific HIF-2 inhibitor in humans. New approaches will be required to target mutant HIF-2 beyond PT2385 or the closely related PT2977 (MK-6482).