Efficacy of PI3K inhibitors in advanced breast cancer

B. Verret, J. Cortes, T. Bachelot, F. Andre, M. Arnedos

    Research output: Contribution to journalReview articlepeer-review

    154 Citations (Scopus)

    Abstract

    The phosphoinositide 3 (PI3)-kinase/Akt signaling pathway has always been a focus of interest in breast cancer due to its role in cell growth, cell proliferation, cell migration and deregulated apoptosis. Its activation has been linked to endocrine resistance and worse prognosis in certain subgroups of breast cancer. In addition, deregulation of the PI3K/Akt pathway including PIK3CA activating mutation is frequently present in breast cancer. Multiple efforts have been carried out to target this pathway, initially with pan-PI3K inhibitors with some hint of activity but hampered by their limiting side-effects. A recent large randomized trial in patients with endocrine-resistant PIK3CA-mutant hormone receptor (HR)-positive tumors led to the approval of the first PI3K inhibitor, alpelisib, in combination with fulvestrant. The specificity of alpelisib against the p110α catalytic isoform provided additional efficacy and a better toxicity profile. In this review, we summarize the main research with PI3K inhibitors in breast cancer and we provide some insight of potential future combinations of this treatment in breast cancer patients.

    Original languageEnglish
    Pages (from-to)x12-x20
    JournalAnnals of Oncology
    Volume30
    Issue number10
    DOIs
    Publication statusPublished - 1 Dec 2019

    Keywords

    • PI3K inhibitors
    • breast cancer
    • targeted therapy

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