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<0.0001). At study day 31, mean tumor volumes (± SE) were 2712.2±37 mm3 in the vehicle group, and 1080.7±49 mm3 in the study group. In addition, animals of the study group received RPT835 from day 31 to day 40 with disease stabilization (no differences in tumor volume between days 31 and 40, P=0.167). The tumor growth curve shows a nearly exponential increase in median tumor volume up to day 31 in the vehicle group and a high rate of slow growing tumors up to day 40 in the study group. In the HS578T xenograft study differences in tumor volume between study and control groups were weak at day 31 (mean tumor volumes ± SE, 703±89.1 mm3 vs. 1053±179.8 mm3, respectively; P<0.001) and at day 40 (1104±162.2 mm3 vs. 1592±335 mm3; P=0.01).

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.