Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients.

摘要: // Hung-Chih Hsu 1, 2 , Tan Kien Thiam 3 Yen-Jung Lu Chien Yuh Yeh 2, 4 Wen-Sy Tsai Jeng Fu You Hsin Yuan Hung Chi-Neu 5 An Hua-Chien Chen Shu-Jen Tsai-Sheng Yang 1 Division of Hematology-Oncology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan College Medicine, University, ACT Genomics, Neihu Dist., Taipei 114, Colon and Rectal Surgery, Graduate Institute Clinical Correspondence to: Chen, e-mail: sjchen@actgenomics.com Yang, a481124@cgmh.org.tw Keywords: BRAF, metastatic colorectal cancer, RAS, mutation, cetuximab resistance Received: July 17, 2015      Accepted: February 18, 2016      Published: March 12, 2016 ABSTRACT Approximately 45% cancer (mCRC) patients with wild-type KRAS exon are resistant to treatment. We set out identify additional genetic markers that might predict the response Fifty-three mCRC were treated cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses 10 EGFR pathway genes analyzed in primary tumors using next-generation sequencing. BRAF PIK3CA (exons 4), NRAS PTEN AKT1 mutations detected 6, 5, 4, patient, respectively. Four non-V600 variants. harbored multiple co-existing (complex) mutations. All complex mutation patterns non-responders. but one harboring Mutations any these three associated poor rate (7.1%) reduced survival (PFS = 8.0 months) compared (74.4% 11.6 months). Our data suggest KRAS, treatment patients.