Polymorphisms in Genes Involved in EGFR Turnover Are Predictive for Cetuximab Efficacy in Colorectal Cancer

摘要: Transmembrane receptors such as the epidermal growth factor receptor (EGFR) are regulated by their turnover, which is dependent on ubiquitin-proteasome-system (UPS). We tested in two independent study cohorts whether single nucleotide polymorphisms (SNPs) genes in-volved EGFR turnover predict clinical outcome cetuximab treated metastatic colorectal can-cer patients. The following SNPs involved degradation were analyzed a screening cohort of 108 patients with chemorefractory setting: c-CBL (rs7105971; rs4938637; rs4938638; rs251837), EPS15 (rs17567; rs7308; rs1065754), NAE1 (rs363169; rs363170; rs363172); SH3KBP1 (rs7051590; rs5955820; rs1017874; rs11795873); SGIP1 (rs604737; rs6570808; rs7526812); UBE2M (rs895364; rs895374); UBE2L3 (rs5754216). showing an association response or survival BRAF and RAS wild-type samples from FIRE-3 study. 153 FOLFIRI plus served valida-tion set, 168 bevacizumab arm controls. FISH was done 138 to test significant associated expression. rs895374 significantly PFS (logrank-p = 0.005; HR 0.60) within No (n=168) could be established (p= 0.56, HR: 0.90). genotype did not affect measurements. recycling interesting mechanism secondary resistance mCRC. This first report suggesting that germline process pre-dict efficacy Genes may new targets treatment