Novel Chemosensitive Single-Nucleotide Polymorphism Markers to Targeted Regimens in Metastatic Colorectal Cancer

作者: Jin C. Kim , Seon Y. Kim , Dong H. Cho , Ye J. Ha , Eun Y. Choi

DOI: 10.1158/1078-0432.CCR-10-1907

关键词:

摘要: Purpose: Methods for predicting individual responsiveness to targeted chemotherapy are urgently needed, considering the frequent resistance and extremely high cost. Experimental Design: A chemosensitive single-nucleotide polymorphism (SNP) discovery schema is presented that utilizes (i) genome-wide SNP screening with a human array an in vitro chemosensitivity assay 118 colorectal cancers, (ii) clinical association analysis other 98 patients who had received metastatic cancer, (iii) biological utility assessment using cell viability assays of transfected cancer (CRC) cells. Results: Nine SNPs related bevacizumab cetuximab regimen sensitivity were chosen during screening. Overall responses regimens revealed carrying TT genotype at ANXA11 rs1049550 or least one G allele LINS1 rs11247226 seemed greater than those C AA genotype, respectively ( P GG DFNB31 rs2274159 LIFR rs3729740 = 0.025 0.07). Cytotoxicity analyses showed all RKO HCT116 CRC clones ISX rs361863 more sensitive T allele, ≤ 0.001–0.024). Conclusions: Chemosensitive markers identified novel three-step process. The candidate marker possibly will hopefully predict responsive regimens, although further validation needed large cohorts. Clin Cancer Res; 17(5); 1200–9. ©2011 AACR .

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