Abstract 2702: Effects of Src and IGF1R inhibition on acquired endocrine therapy resistant breast cancer

Effective standard therapy for hormone receptor-positive (HR+) breast cancer targets the estrogen receptor (ER). However, a significant proportion of women with HR+ breast cancer relapse. Furthermore, the majority of women with metastatic HR+ breast cancer develop resistance to endocrine therapy. Adaptive cross-talk between ER and growth factor receptor pathways including IGF1R and Src is involved in acquired endocrine therapy resistance. To determine effects of adding dasatinib (D), Src inhibitor, and/or anti-IGF1R Ab MK0646 (M) to the ER antagonist fulvestrant (F) in an acquired endocrine therapy resistant breast cancer, we used long-term estrogen-deprived (LTED) derivative of ER+ breast cancer cell lines, MCF-7/LTED and HCC-1428/LTED. Parental and LTED cells were treated with variable combinations of F, D and M, followed by determinations of drug effects on cell growth, migration, and invasion in vitro and tumor growth in vivo. We demonstrated that LTED cells were resistant to F alone, comparing parental cells (P