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

Courtney, Kevin D.; Ma, Yuanqing; Diaz de Leon, Alberto; Christie, Alana; Xie, Zhiqun; Woolford, Layton; Singla, Nirmish; Joyce, Allison; Hill, Haley; Madhuranthakam, Ananth J.; Yuan, Qing; Xi, Yin; Zhang, Yue; Chang, Jenny; Fatunde, Oluwatomilade; Arriaga, Yull; Frankel, Arthur E.; Kalva, Sanjeeva; Zhang, Song; McKenzie, Tiffani; Reig Torras, Oscar; Figlin, Robert A.; Rini, Brian I.; McKay, Renée M.; Kapur, Payal; Wang, Tao; Pedrosa, Ivan; Brugarolas, James

doi:10.1158/1078-0432.ccr-19-1459

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

Purpose: The heterodimeric transcription factor HIF-2 is arguably the most important driver of clear cell renal cell carcinoma (ccRCC). Although considered undruggable, structural analyses at the University of Texas Southwestern Medical Center (UTSW, Dallas, TX) identified a vulnerability in the …