Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients

摘要: The anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (moAbs) cetuximab or panitumumab are administered to colorectal cancer (CRC) patients who harbor wild-type RAS proto-oncogenes. However, a percentage of do not respond this treatment. In addition mutations in the genes, other such as BRAF, PI3KCA, PTEN, could be involved resistance anti-EGFR moAb therapy. order develop comprehensive approach for detection and eventually identify genes responsible moAbs, we investigated panel 21 by parallel sequencing on Ion Torrent Personal Genome Machine platform. We sequenced 65 CRCs that were treated with panitumumab. Among these, 37 samples responsive 28 resistant. confirmed EGFR-pathway (KRAS, NRAS, PI3KCA) relevant conferring therapy predict response (p = 0.001). After exclusion KRAS, BRAF PI3KCA combined still significantly associate resistant phenotype (p = 0.045, Fisher exact test). addition, FBXW7 SMAD4 prevalent cases non-responsive moAb. all (excluding KRAS), ability improved (p = 0.002, combination at KRAS five gene demonstrates usefulness feasibility multigene assess moAbs. application technology clinical practice, its innate simultaneously examine genetic status several proved more accurate sensitive than presently use traditional approaches.