Precision Targeting of Mutant PI3Kα in Cancer by Selective Degradation

Bart Vanhaesebroeck; John E Burke; Ralitsa R Madsen

doi:10.1158/2159-8290.CD-21-1411

Precision Targeting of Mutant PI3Kα in Cancer by Selective Degradation

Cancer Discov. 2022 Jan;12(1):20-22. doi: 10.1158/2159-8290.CD-21-1411.

Authors

Bart Vanhaesebroeck¹, John E Burke^{2

3}, Ralitsa R Madsen⁴

Affiliations

¹ University College London Cancer Institute, University College London, London, United Kingdom. bart.vanh@ucl.ac.uk.
² Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
³ Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
⁴ University College London Cancer Institute, University College London, London, United Kingdom.

Abstract

PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently genetically activated kinases in solid tumors. In this issue of Cancer Discovery, Song and colleagues report that the related PI3Kα inhibitors taselisib and inavolisib trigger receptor tyrosine kinase (RTK)-dependent degradation of the mutant p110α protein in breast cancer cells that are positive for HER2 RTK, limiting feedback-mediated drug resistance and potentially widening the therapeutic index of PI3Kα inhibition.See related article by Song et al., p. 204.

Publication types

Research Support, Non-U.S. Gov't
Comment

MeSH terms

Class I Phosphatidylinositol 3-Kinases / genetics
Humans
Neoplasms* / drug therapy
Neoplasms* / genetics
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use

Substances

Protein Kinase Inhibitors
Class I Phosphatidylinositol 3-Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding