Abstract 5532: Folate receptor expression in human malignancies to select patients who would benefit from folate conjugated therapy

Abstract

Abstract The folate receptor (FR) is expressed on a number of human tumors, including ovarian, renal, lung, and breast. Folic acid is the ligand for the FR and many innovative strategies for targeting therapeutics to tumors make use of this ligand/receptor pair. Novel therapeutic approaches include folate conjugation to cytotoxics or radiopharmaceuticals, folate-coated liposomes containing antisense oligonucleotides, folate conjugates of pro-drugs, and folate-linked nanoparticle carriers for therapeutic drugs and genes. Potential patient enrichment strategies are necessary to allow for better targeting of these agents to those patients who have FR expressing tumors. Preclinical experiments to evaluate the molecular correlation of FR levels by three different methods, qRT-PCR, IHC, and the radiolabeled ligand binding assay, were conducted. A total of seventeen samples (four xenografts and thirteen primary patient ovarian and endometrial tumor biopsies) were evaluated for FR expression in these three independent assays and the FR levels correlated in this sample size. Compared to a preclinical model that was sensitive to epothilone-folate conjugate therapy, most patient samples expressed higher FR levels. These data provide a reliable and useful method to identify patient tumors that express the FR above a baseline determined to be sufficient for response to folate-conjugated therapy in preclinical models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5532.