Targeting PIK3CA mutant breast cancer with the combination of PIK3CA-specific inhibitor, BYL719, and IGF1-R antibody, ganitumab.

e13525 Background: PI3K/AKT signaling is a critical growth and survival pathway in many human cancers. PI3Ks are lipid kinases that are important in controlling signaling pathways involved in cell proliferation, motility, cell death and cell invasion. The α isoform of PI3K (PIK3CA) is linked upstream mainly to receptor tyrosine kinases and is commonly mutated in various solid tumor types. The existing scientific evidence strongly supports the concept of targeting PIK3CA in human cancers, especially those harboring PIK3CA mutations. Sustained PIK3CA inhibition may lead to aberrant RTK signaling to attenuate PIK3CA inhibition. IGF1R is a RTK commonly expressed in human neoplasia. Its signaling has been implicated in tumor cell survival. Additionally, IGF1R/IRS signaling has been shown to be a feedback pathway to down-modulate mTOR inhibition by RAD001 in cancer cells. We reason that the efficacy of PIK3CA inhibition would be enhanced if PIK3CA inhibitor is combined with a targeted agent against a key RTK in...