Sorafenib and cetuximab therapy led to a mixed radiographic response with some areas showing dramatic improvement and other areas showing stable disease over a 7-month period which is a notably long period of progression-free survival for V600EBRAF mutated colon cancer.
Female patients and older group harbored a higher KRAS mutation (P = 0.018 and P = 0.031, respectively); BRAF (V600E) mutation showed a higher frequency in colon cancer and poor differentiation tumors (P = 0.020 and P = 0.030, respectively); proximal tumors appeared a higher PIK3CA mutation (P<0.001) and distant metastatic tumors shared a higher NRAS mutation (P = 0.010).
The clinical studies in the manuscript by Al-Marrawi et al. describe the rational combination of signaling inhibitors in a colon cancer patient whose tumor cells express a mutant active B-RAFV600E protein that signals into the MEK1/2-ERK1/2 pathway downstream of K-RAS; this is a particularly aggressive form of colon cancer for which few rational therapeutic interventions have been available until recent times.
There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer.
Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing.
Herein, we present the case of a patient with bulky V600E-mutant BRAF hepatic flexure colon carcinoma, treated initially with FOLFOX plus bevacizumab neoadjuvant therapy and surgery.
We have tested a battery of melanoma and colon carcinoma cell lines that carry mutations in BRAF, NRAS and KRAS genes and have observed that those with NRAS and KRAS mutations are more sensitive to killing by IPA3.
A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type) and to construct a gene expression-based classifier for detecting BRAF mutant samples with high sensitivity.
This study shows that BRAF mutations profiled from stage II and III colon cancer tumors were associated with poor SAR and validates and explains, at least in part, previous observations associating it with poor OS.
Convincing data on colon carcinoma will be demonstrated at ESMO 2012 with the conclusion to screen patients for BRAFV600E for enrolment in an upcoming clinical trial combining BRAF and EGFR inhibitors.
We determined the effects on clinical outcome of the BRAF mutation, microsatellite instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma.
The CpG island methylator phenotype (CIMP-high, CIMP1) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer.
These results indicate that molecular analysis for BRAF may be a useful biomarker for identifying patients with right-sided colon cancer with poor outcome who may benefit from a more individualized course of therapy.
Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.
For these reasons, BRAF mutations may be considered a key genetic factor for the metastatic progression of PTC and also for other tumors such as melanoma and colon cancer and a new BRAF-specific therapeutic strategy was already suggested.
These data suggest that the BRAFV600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer.