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Expression Of FGFR2b In Gastric Cancer As Measured By Immunohistochemistry With A Highly Specific Monoclonal Antibody

2014-09-16 21:37:36

American Association for Cancer Research; 7 APR 2014; Abstract Number 2845



Amit M. Deshpande, Servando Palencia, David I. Bellovin, Abigael T. Gemo, Tina Giese, Bradley Stohr, Kristen L. Pierce, Gerrit Los



Background



Gastric cancer is the second leading cause of death from cancer worldwide. Amplification of the FGFR2 oncogene has been reported in 3 to 9% of gastric cancers, and several studies have also reported overexpression of the FGFR2 protein in about 15-35% of the cases using immunohistochemistry (IHC). Both amplification of the FGFR2 gene and overexpression of the FGFR2b protein have been shown to correlate with an aggressive disease phenotype, making FGFR2 an attractive therapeutic target.



Two FGFR2 isoforms have been implicated in cancer: FGFR2b and FGFR2c. Five Prime Therapeutics has developed a therapeutic antibody, FPA144, which specifically targets the FGFR2b isoform for use in treatment of gastric cancer patients with FGFR2 amplification and is associated with tumor regression in xenograft models with FGFR2-amplified cell lines. Additionally, FPA144 targets cells with FGFR2b overexpression. In a report describing FPA144, presented at this meeting (Abstract #5446, AACR 2014), we show that tumors with FGFR2 amplification predominantly express the b-isoform.



It is known that overexpression of oncogenes can occur in the absence of DNA amplification. To test if FGFR2 follows this paradigm, and to identify potential patients for treatment with FPA144, Five Prime Therapeutics generated a monoclonal antibody, FPR2-D, for use as a companion IHC diagnostic (CDx) for selecting patients with high levels of FGFR2b protein. Using this antibody, we show that an additional 10.8% (3+ IHC score) of gastric cancer cases express FGFR2b, a cohort of patients that could potentially benefit from FPA144.



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