STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Overview

Journal Cancer Discov

Specialty Oncology

Date 2023 Aug 25

PMID 37623743

Authors

Leonard Buckbinder

David J St Jean Jr

Trang Tieu

Brendon Ladd

Brendan Hilbert

Weixue Wang

Jacob T Alltucker

Samantha Manimala

Gregory V Kryukov

Natasja Brooijmans

Gregory Dowdell

Philip Jonsson

Michael Huff

Angel Guzman-Perez

Erica L Jackson

Marcus D Goncalves

Darrin D Stuart

Affiliations

Soon will be listed here.

Abstract

Significance: These preclinical data demonstrate that the mutant-selective, allosteric PI3Kα inhibitor STX-478 provides robust efficacy while avoiding the metabolic dysfunction associated with the nonselective inhibitor alpelisib. Our results support the ongoing clinical evaluation of STX-478 in PI3Kα-mutated cancers, which is expected to expand the therapeutic window and mitigate counterregulatory insulin release. See related commentary by Kearney and Vasan, p. 2313. This article is featured in Selected Articles from This Issue, p. 2293.

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