HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans
Abstract
HIF2α is a key driver of kidney cancer. Using a belzutifan analogue (PT2399), we previously showed in tumorgrafts (TG) that ∼50% of clear cell renal cell carcinomas (ccRCC) are HIF2α dependent. However, prolonged treatment induced resistance mutations, which we also identified in humans. Here, we evaluated a tumor-directed, systemically delivered, siRNA drug (siHIF2) active against wild-type and resistant-mutant HIF2α.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 29, 2022
- Source ID
- 10.1158/1078-0432.ccr-22-0963
Entities
People
- Akhilesh Mishra
- Alana Christie
- Alexander Ivanishev
- Allison Joyce
- Alyssa Macchiaroli
- Christina Stevens
- Daniel Li
- Deyssy Carrillo
- Faeze Saatchi
- Ivan Pedrosa
- James Brugarolas
- James Hamilton
- Jeffrey Miyata
- Layton Woolford
- Olivia Brandenburg
- Oluwatomilade Fatunde
- Oreoluwa Onabolu
- Payal Kapur
- Qing Zhang
- Qurratulain Yousuf
- Quyen N. Do
- So C. Wong
- Steven B. Kanner
- Tanner Hardy
- Thomas Schluep
- Tiffani McKenzie
- Vanina T. Tcheuyap
- Wei He
- Yuanqing Ma
Organizations
- Congressionally Directed Medical Research Programs
- National Cancer Institute
- University of Texas Southwestern Medical Center
- University of Texas at Austin