The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib

Tao Shen; Xueqing Hu; Xuan Liu; Vivek Subbiah; Blaine H.M. Mooers; Jie Wu

doi:10.1038/s41698-021-00188-x

The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib

Tao Shen, Xueqing Hu, Xuan Liu, Vivek Subbiah, Blaine H.M. Mooers, Jie Wu

Investigational Cancer Therapeutics

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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.

Original language	English (US)
Article number	48
Journal	npj Precision Oncology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s41698-021-00188-x
State	Published - Dec 2021

ASJC Scopus subject areas

Cancer Research
Oncology

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title = "The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib",

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.",

author = "Tao Shen and Xueqing Hu and Xuan Liu and Vivek Subbiah and Mooers, {Blaine H.M.} and Jie Wu",

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AU - Hu, Xueqing

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AU - Subbiah, Vivek

AU - Mooers, Blaine H.M.

AU - Wu, Jie

PY - 2021/12

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AB - 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.

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The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib

Abstract

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