Antitumor activities of bevacizumab for KRAS, BRAF, and PIK3CA mutated human colorectal cancer xenograft models.

362 Background: In colorectal cancer, it has been reported that mutations (mts) in KRAS, BRAF, or PIK3CA can have a negative impact on molecular target therapies. Especially, a KRAS mt represents a predictive biomarker for resistance to anti-EGFR antibodies. Bevacizumab (BV), an anti-VEGF-A antibody, has been demonstrated to have clinical benefits in colorectal cancers; however, the impact of mts in especially BRAF or PIK3CA on the efficacy of BV remains unknown. In this study, we examined the antitumor activity of BV in human colorectal cancer xenograft models harboring these mts. Methods: BALB-nu/nu mice were subcutaneously inoculated with 15 colorectal cancer cell lines. BV was intraperitoneally administered every week for 3 weeks at a dose of 5 mg/kg. Antitumor activity was evaluated by determining tumor volume and tumor growth inhibition (TGI) on day 22. The colorectal cancer cell lines used were screened for KRAS, BRAF, and PIK3CA mts by direct sequencing of hot spots. Statistical analysis was perfo...