HIF2 inactivation and tumor suppression with a tumor-directed RNA-silencing drug in mice and humans.
Yuanqing MaAllison JoyceOlivia BrandenburgFaeze SaatchiChristina StevensVanina Toffessi TcheuyapAlana ChristieQuyen N DoOluwatomilade FatundeAlyssa MacchiaroliSo C WongLayton WoolfordQurratulain YousufJeffrey MiyataDeyssy CarrilloOreoluwa OnaboluTiffani McKenzieAkhilesh MishraTanner HardyWei HeDaniel LiAlexander IvanishevYang ZhangIvan PedrosaPayal KapurThomas SchluepSteven B KannerJames HamiltonJames BrugarolasPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2022)
To our knowledge, this is the first example of functional inactivation of an oncoprotein and tumor suppression with a systemic, tumor-directed, RNA-silencing drug. These studies provide a proof-of-principle of HIF2α inhibition by RNA-targeting drugs in ccRCC and establish a paradigm for tumor-directed RNA-based therapeutics in cancer.