PI3K inhibition circumvents resistance to SHP2 blockade in metastatic triple-negative breast cancer.

ABSTRACT: The protein tyrosine phosphatase SHP2 activates oncogenic pathways downstream of most receptor tyrosine kinases (RTK) and has been implicated in various cancer types, including the highly aggressive subtype of triple-negative breast cancer (TNBC). Although allosteric inhibitors of SHP2 have been developed and are currently being evaluated in clinical trials, neither the mechanisms of the resistance to these agents, nor the means to circumvent such resistance have been clearly defined. The PI3K signaling pathway is also hyperactivated in breast cancer and contributes to resistance to anticancer therapies. When PI3K is inhibited, resistance also develops for example via activation of RTKs. We therefore assessed the effect of targeting PI3K and SHP2 alone or in combination in preclinical mode

SUBMITTER: Amante RJ 

PROVIDER: S-EPMC10256672 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature