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Combined RAF and EGFR inhibition leads to improved in vivo efficacy in BRAF-mutant colorectal cancer. Combined RAF and EGFR inhibition leads to improved.

Published byΠιλάτος ŌἈβαδδών Κόρακας Modified over 6 years ago

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Presentation on theme: "Combined RAF and EGFR inhibition leads to improved in vivo efficacy in BRAF-mutant colorectal cancer. Combined RAF and EGFR inhibition leads to improved."— Presentation transcript:

1 Combined RAF and EGFR inhibition leads to improved in vivo efficacy in BRAF-mutant colorectal cancer. Combined RAF and EGFR inhibition leads to improved in vivo efficacy in BRAF-mutant colorectal cancer. A, BRAF-mutant colorectal cancer xenografts derived from HT-29 and WiDr cells were treated with vehicle only (CON), vemurafenib only (VEM, 75 mpk twice daily), erlotinib (ERL, 100 mpk daily), or both inhibitors (VEM/ERL) in combination for 21 days. Average percent change in tumor volume relative to initial tumor volume is shown. Error bars represent SEM. **P < for combined vemurafenib/erlotinib vs. all other treatment groups. B, waterfall plots showing the percent change in volume (relative to initial tumor volume) for the individual tumors in each treatment group. C, tumor tissue from HT-29 xenografts treated for 3 days as indicated was evaluated by IHC for P-ERK and a marker of cell proliferation (Ki67). Tumors were harvested 4 hours after dosing on day 3. D, levels of P-EGFR were assessed in human BRAF-mutant colorectal cancers (CRC) and melanomas by IHC. Representative examples are shown. Colorectal cancer cases with the lowest (C3) and highest (C7) P-EGFR levels are shown. A total of 60% of BRAF-mutant colorectal cancers (n = 10) exhibited high levels of P-EGFR, whereas only 18% of BRAF-mutant melanomas (n = 11) exhibited high levels of P-EGFR (P < 0.05). Ryan B. Corcoran et al. Cancer Discovery 2012;2: ©2012 by American Association for Cancer Research

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