Abstract 3923: A role for fibroblast growth factor receptors in growth of atypical teratoid rhabdoid tumor cells and as potential therapeutic targets

Abstract

Abstract Malignant rhabdoid tumors are characterized by the loss of the SWI/SNF complex subunit SMARCB1. Atypical Teratoid Rhabdoid Tumor (ATRT) is a rare form of pediatric MRT that occurs in the CNS. Current treatment modalities for this tumor type continue to be surgical resection, chemotherapy and radiotherapy, but overall survival is still relatively low for younger children with this disease. We initially tested the sensitivity of three ATRT cell lines to 48 chemotherapeutic agents and selective inhibitors. Our results indicated that two cell lines CHLA-04-ATRT and CHLA-05-ATRT were sensitive to FGFR inhibition. Further analysis of a panel of five ATRT cell lines indicated that the cell lines CHLA-04-ATRT, CHLA-05-ATRT, CHLA-266 and BT-12 were sensitive to the FGFR inhibitors PD173074, BGJ398 and AZD4547. Interestingly, the ATRT cell line CHLA-06-ATRT did not show sensitivity to FGFR inhibition. Analysis of FGFR protein expression by immunoblot analysis indicated that CHLA-04-ATRT and CHLA-266 cells expressed both FGFR1 and FGFR2, while the cell lines CHLA-05-ATRT and BT-12 expressed only FGFR1. The CHLA-06-ATRT cell line did not show expression of any FGFRs. We further demonstrated functional FGFR activity in the ATRT cell lines by treating growth factor-deprived ATRT cells with FGF-1 or FGF-2, both of which led to dose dependent cell growth only in the cell lines expressing FGFR1 or FGFR2. We are currently investigating the expression of FGFR isoforms in ATRT patient samples. Taken together, our results demonstrate a potential role for FGFR1 and FGFR2 in the survival and proliferation of ATRT cells and indicate that FGFRs could serve as potential targets for therapy in ATRT. Citation Format: David O. Azorsa, Oliver B. Pepper, Madhavi Chakravadhanula, David W. Lee, Justin J. Montoya, Victor Ozols, Ratan Bhardwaj, Robert J. Arceci. A role for fibroblast growth factor receptors in growth of atypical teratoid rhabdoid tumor cells and as potential therapeutic targets. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3923. doi:10.1158/1538-7445.AM2015-3923