Unbiased screening reveals that blocking exportin 1 overcomes resistance to PI3Kα inhibition in breast cancer

摘要

Targeting PI3K is a promising approach for cancer therapy, andthe PI3Kα-selective inhibitor alpelisib has been approved forbreast cancer treatment.1–3 However, the development ofacquired resistance poses a significant clinical challenge. Loss ofPTEN and activation of mTOR, CDK4/6, or PIM have been reportedto mediate acquired resistance to alpelisib.4–7 The mechanismsleading to resistance to PI3Kα inhibitors appear to be differentunder different circumstances, and the aforementioned strategiesmay be beneficial for a particular group of patients. New strategiesto overcome acquired resistance in a broad spectrum of patientsneed to be discovered.