Abstract 3805: Novel chemosensitive single-nucleotide polymorphism markers to targeted regimens in metastatic colorectal cancer

Purpose: Methods for predicting individual responsiveness to targeted chemotherapy are urgently needed, considering the frequent resistance and extremely high cost of such therapies. Experimental Design: A chemosensitive single-nucleotide polymorphism (SNP) discovery schema is presented that utilizes genome-wide SNP screening with a human SNP array, an in vitro chemosensitivity assay in 118 colorectal cancers, clinical association analysis in 98 patients who had received metastatic chemotherapy, and biological utility assessment using cell viability assays of transfected colorectal cancer (CRC) cells. Results: Eleven SNPs related to bevacizumab and cetuximab sensitivity were initially chosen during screening. Response rates and survival periods revealed that patients carrying specific alleles of the SNPs ANXA11 rs1049550, LINS1 rs11247226, or ITGA3 rs2230392 were chemosensitive to bevacizumab regimens, and patients with DFNB31 rs2274159, LIFR rs3729740, or ISX rs361863 were chemosensitive to cetuximab regimens. Cytotoxicity analyses using MTT and caspase-3 assays showed that all RKO and HCT116 CRC clones transfected with the reference alleles of LIFR rs3729740 and ISX rs361863 (G and C, respectively) were more sensitive to cetuximab regimens than those transfected with the substitution alleles. Conclusions: Chemosensitive SNP markers were identified using a novel three-step process. The chemosensitive markers LIFR rs3729740 and ISX rs361863 will hopefully predict responsive patients to cetuximab regimens, although further validation is needed in large cohorts. 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 3805. doi:10.1158/1538-7445.AM2011-3805