February 8, 2024Open Access

Data from Allosteric PI3Kα Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations

View Full Paper

Ask AI

Bookmark

Authors

AVAndreas VarkarisBeth Israel Deaconess Medical Center FCFerran Fece de la CruzHarvard University EMElizabeth E. MartinBroad Institute

Discussion

Member takes

Implication

Genomic analysis reveals secondary PIK3CA mutations drive resistance to alpelisib in advanced breast cancer, indicating that allosteric PI3Kα inhibitors overcome this barrier.

Key Points

Novel allosteric PI3Kα inhibitor RLY-2608 overcomes drug resistance mediated by secondary PIK3CA binding pocket alterations in advanced breast cancer.
Serial liquid biopsies and rapid autopsies in 39 patients revealed that 50% acquired pathway alterations, including PTEN loss and AKT1 mutations.
Targeting PIK3CA mutations with allosteric inhibitors highlights a viable therapeutic strategy to counter orthosteric PI3Kα inhibitor resistance.

Cite This Study

Varkaris et al. (2024) studied this question.

synapsesocial.com/papers/68e7b92eb6db64358770f11b https://doi.org/10.1158/2159-8290.c.7065313.v1

View Full Paper

Ask AI

Bookmark

Implication

Genomic analysis reveals secondary PIK3CA mutations drive resistance to alpelisib in advanced breast cancer, indicating that allosteric PI3Kα inhibitors overcome this barrier.

Data from Allosteric PI3Kα Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations

Discussion

Member takes

Implication

Key Points

Cite This Study

Data from Allosteric PI3Kα Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider