Article
Allosteric PI3Kα Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations.
Cancer discovery - 8 Feb 2024
Varkaris Andreas, Fece de la Cruz Ferran, Martin Elizabeth E, Norden Bryanna L, Chevalier Nicholas, Kehlmann Allison M, Leshchiner Ignaty, Barnes Haley, Ehnstrom Sara, Stavridi Anastasia-Maria, Yuan Xin, Kim Janice S, Ellis Haley, Papatheodoridi Alkistis, Gunaydin Hakan, Danysh Brian P, Parida Laxmi, Sanidas Ioannis, Ji Yongli, Lau Kayao, Wulf Gerburg M, Bardia Aditya, Spring Laura M, Isakoff Steven J, Lennerz Jochen K, Del Vecchio Kathryn, Pierce Levi, Pazolli Ermira, Getz Gad, Corcoran Ryan B, Juric Dejan
Abstract excerpt
PIK3CA mutations occur in ∼8% of cancers, including ∼40% of HR-positive breast cancers, where the PI3K-alpha (PI3Kα)-selective inhibitor alpelisib is FDA approved in combination with fulvestrant. Although prior studies have identified resistance mechanisms, such as PTEN loss, clinically acquired resistance to PI3Kα inhibitors remains poorly understood. Through serial liquid biopsies and rapid autopsies in 39...
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