The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
- Resource Type
- article
- Authors
- Tao Shen; Xueqing Hu; Xuan Liu; Vivek Subbiah; Blaine H. M. Mooers; Jie Wu
- Source
- npj Precision Oncology, Vol 5, Iss 1, Pp 1-4 (2021)
- Subject
- Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
- Language
- English
- ISSN
- 2397-768X
Abstract Recently Food and Drug Administration (FDA)-approved pralsetinib (BLU-667) and selpercatinib (LOXO-292) are RET-selective protein tyrosine kinase inhibitors for treating RET-altered cancers, but whether they have distinct activity was unknown. The L730V/I mutations at the roof of the solvent-front site of the RET kinase were identified as strongly resistant to pralsetinib but not to selpercatinib. Selpercatinib effectively inhibited these mutants and the KIF5B-RET(L730V/I) oncogene-driven tumors.