Abstract P5-02-01: FGFR Signalling Drives the Growth of Triple Negative and Basal-Like Breast Cancer Cell Lines Both In Vitro and In Vivo

Abstract

Abstract Background: Substantial evidence now links aberrant signalling by the fibroblast growth factor receptors (FGFRs) to the development of multiple different cancer types. The oncogenic drivers of triple negative and basal-like breast cancers are largely unknown and we examined for a potential role of FGFR signalling in the oncogenesis of triple negative breast cancer. Methods: We examined the sensitivity of a panel of 40 breast cancer cell lines to the selective fibroblast growth factor receptor (FGFR) inhibitor PD173074. Results: Triple negative (TN) breast cancer cell lines were more sensitive to PD173074 than comparator cell lines (p=0.0028), with half (8/16) of TN cell lines demonstrating significantly reduced growth. The majority of TN cell lines demonstrated only modest sensitivity to FGFR inhibition in two-dimensional growth, but were highly sensitive in anchorage independent conditions. PD173074 inhibited down stream MAPK signalling and induced cell cycle arrest and apoptosis. Basal-like breast cancer cell lines were found to express autocrine FGF2 ligand, and RNA interference targeting of FGF2 significantly reduced anchorage independent growth. Finally, PD173074 significantly reduced the growth of basal-like breast cancer cell line xenografts. Conclusion: Basal-like breast cancer cell lines express autocrine FGF2 and demonstrate substantial sensitivity to FGFR inhibitors, identifying a potential novel therapeutic approach for these cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-02-01.