Abstract P6-02-07: Targeting triple-negative breast cancer with fibroblast growth factor receptor 2 allosteric inhibitor RPT835

Background: FGFR2 is amplified in 4% of triple-negative breast cancers (TNBC). In addition, the mRNA expression levels of FGFR2 were significantly increased in amplified vs nonamplified tumor samples, suggesting a potential role for FGFR2 in TNBC (Turner et al. 2010). We evaluated efficacy of allosteric inhibition of FGFR2 in high- and low-expressing TNBC xenografts. Methods: Immunocompromised mice were used for xenotransplantation of FGFR2 high-expressing TNBC cells (SUM52PE) or FGFR2 low-expressing TNBC cells (HS578T). Forty animals with measurable tumors were selected on day 10 and randomized into treatment groups (low-molecular weight allosteric inhibitor RPT835, 30 mg/kg; gavage, daily) or vehicle (water; gavage, daily). Measurements of tumor volume (mm3) were performed by digital calipers every 3 days during 40 days after tumor inoculation. Results: RPT835 significantly inhibited aggressive growth of SUM52PE tumor xenograft (P Conclusions: The allosteric FGFR2 inhibitor RPT835 significantly impacts on growth of FGFR2-expressing TNBC. Citation Format: Sergey A Tjulandin, Ilya V Tsimafeyeu, Mikhail Y Byakhov, Wei Yin, John Ludes-Meyers, Frits Daeyaert. Targeting triple-negative breast cancer with fibroblast growth factor receptor 2 allosteric inhibitor RPT835 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-07.