EGFR amplification and PI3K pathway mutations identify a subset of breast cancers that synergistically respond to EGFR and PI3K inhibition.

ABSTRACT: EGFR family receptor tyrosine kinase signaling is commonly dysregulated in cancer by amplification or activating mutations. Although studies have investigated dual EGFR/PI3K inhibition in breast cancer, they have not determined biomarkers which predict success. We present evidence of a patient subset with EGFR amplification and PI3Kinase pathway mutations in breast cancer which can be synergistically targeted by dual EGFR/PI3K inhibition. This study identified that EGFR amplification occurs in ~1-5% of breast cancer patients with shorter overall survival compared to unamplified patients. Up to 71% of EGFR amplified tumors have activating mutations in the PI3K pathway. Dual EGFR/PI3K inhibition more dramatically reduced mTOR and AKT signaling in BT20 and MDA-MB-468 cells which both have EGF

SUBMITTER: Wisniewski DJ 

PROVIDER: S-EPMC12714574 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature