Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment

Pharmacogenomics
Lydia Wt Cheung, Gordon B Mills

Abstract

The regulatory subunit of PI3K, p85α (encoded by PIK3R1), binds, stabilizes and inhibits the PI3K p110 catalytic subunit. Functional characterization of PIK3R1 mutations has identified not only hypomorphs with reduced inhibition of p110, but also hypomorphs and dominant negative mutants that disrupt a novel regulatory role of p85α on PTEN or neomorphs that activate unexpected signaling pathways. The diverse phenotypic spectrum of these PIK3R1 driver mutations underscores the need for different treatment strategies targeting tumors harboring these mutations. This article describes the functional consequences of the spectrum of PIK3R1 driver mutations and therapeutic liabilities they may engender.

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Citations

Mar 21, 2017·ELife·Mohammad Hossein RohbanAnne E Carpenter
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ebubekir Dirican, Mustafa Akkiprik
Aug 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sushant KumarMark B Gerstein
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Feb 16, 2019·International Journal of Molecular Sciences·Rita SeeboeckJohannes Haybaeck
Sep 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xinran LiLydia W T Cheung

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Methods Mentioned

BETA
xenografts
GTPases
ubiquitination

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