PTEN Loss Mediates Clinical Cross-Resistance to CDK4/6 and PI3Kα Inhibitors in Breast Cancer

PTEN 缺失介导乳腺癌对 CDK4/6 和 PI3Kα 抑制剂的临床交叉耐药性

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作者:Carlotta Costa #, Ye Wang #, Amy Ly, Yasuyuki Hosono, Ellen Murchie, Charlotte S Walmsley, Tiffany Huynh, Christopher Healy, Rachel Peterson, Shogo Yanase, Charles T Jakubik, Laura E Henderson, Leah J Damon, Daria Timonina, Ioannis Sanidas, Christopher J Pinto, Mari Mino-Kenudson, James R Stone, Nic

Significance

Our analysis of serial biopsies uncovered RB and PTEN loss as mechanisms of acquired resistance to CDK4/6 inhibitors, utilized as first-line treatment for ER-positive advanced breast cancer. Importantly, these findings have near-term clinical relevance because PTEN loss also limits the efficacy of PI3Kα inhibitors currently approved in the post-CDK4/6 setting.This article is highlighted in the In This Issue feature, p. 1.

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