The effect of the alpha-specific PI3K inhibitor alpelisib combined with anti-HER2 therapy in HER2+/PIK3CA mutant breast cancer.

ABSTRACT:

Background

HER2 is amplified or overexpressed in around 20% of breast cancers (BC). HER2-targeted therapies have significantly improved the prognosis of patients with HER2+ BC, however, de novo and acquired resistance to anti-HER2 treatment is common. Activating mutations in the PIK3CA gene are reported in ∼30% of HER2+ BC and are associated with resistance to anti-HER2 therapies and a poor prognosis. Here, we investigated the in vitro and in vivo antitumor efficacy of the alpha-specific PI3K inhibitor alpelisib alone or in combination with anti-HER2 therapy using a panel of HER2+ BC cell lines. We also generated models of acquired resistance to alpelisib to investigate the mechanisms underlying resistance to alpha-specific PI3K inhibition.

Materials

SUBMITTER: Cataldo ML 

PROVIDER: S-EPMC10353540 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature