KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model.

摘要: BACKGROUND: The treatment of metastatic colorectal cancer (mCRC) includes drugs targeting the epidermal growth factor receptor (EGFR). Mutation in codon 12 or 13 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, downstream EGFR, evokes constitutive activation RAS/RAF/MAPK signaling pathway and correlates with resistance to anti-EGFR monoclonal antibody (mAb) therapies. However, a retrospective study reported that proportion patients KRAS G13D mutation may respond cetuximab. A similar analysis for panitumumab was not as conclusive. We sought determine sensitivity CRC cell lines cetuximab investigate correlation mutational status responsiveness panitumumab. METHODS: To panitumumab, were treated an optimized concentration each mAb, proliferation assays conducted. RESULTS: After at optimum 8 g/well, mutant HCT-116, LoVo, T84 showed intermediate both treatments, between resistant G12V line SW480 sensitive wild-type LIM1215. One significantly more than (P .02). CONCLUSION: specific determines treatment, corresponding clinical observations. Gastrointest Cancer Res 7:23‐26. © 2014 by International Society Gastrointestinal Oncology