Abstract 595: E-3810 antitumor activity in human xenografts expressing different levels of FGF receptor 1

Abstract

Abstract E-3810 is a novel small molecule that selectively inhibits VEGF receptor-1, -2 and -3 and FGF receptor-1 (FGFR-1) tyrosine kinases currently undergoing a Phase 1 clinical trial in Europe. We have previously shown that the compound has strong anti-angiogenic effects in vivo and displays potent activity in all the human xenograft models in which it has been tested. We have also recently demonstrated that interference with FGF/FGFR pathway could result in a higher drug cytotoxic activity in those cell lines whose growth in vitro was dependent on the pathway. In order to corroborate these findings in an in vivo setting, a panel of human xenografts characterized by different expression of FGFR-1and FGF2 ligand is being screened for the response to E-3810 given at its optimal dose (20 mg/kg per os daily). Athymic female mice were transplanted s.c. with the different human xenografts and, when tumor masses reached the size of 80-120 mg, were randomized to receive vehicle or E-3810 for 14 days. Results are available for 7 models (see table reported below). All the selected tumors displayed similar growth rates, except for RXF_486 that grew more slowly. Tumor growth resumed upon drug withdrawal, at a rate seemingly higher where FGFR-1 was highly expressed. These preliminary results confirm the strong activity of E-3810 in a large panel of tumours, with growth control and, sometimes, regressions. Studies are ongoing to enlarge the panel of models and to confirm the observed trend suggesting a somewhat higher sensitivity to E-3810 in tumors expressing higher FGFR-1 and\or FGF ligand. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 595. doi:10.1158/1538-7445.AM2011-595