Current clinical guidelines recommend mutation analysis for select codons in KRAS and NRAS exons 2, 3, and 4 and BRAFV600E to guide therapy selection and prognostic stratification in advanced colorectal cancer.
Pfizer announced plans to acquire Array BioPharma, maker of a BRAF-MEK inhibitor combination that is currently approved for melanoma and could become a first-in-class treatment for colorectal cancer.
Previous studies have reported that rafoxanide, as an inhibitor of BRAFV600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer.
Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial.
In fact, the discordant pattern of BRAF and KRAS ctDNA was significantly correlated with the clinical response of melanoma to pembrolizumab treatment and progression of colorectal cancer noted by PET and/or CT scan.
Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer.
We conducted a systematic review and meta-analysis of the additive effect of biologic agents to adjuvant chemotherapy on survival in colorectal cancer (all comers and subpopulations defined by microsatellite instability, BRAF and KRAS status, and stage).
Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Assessing functional and molecular consequences of pharmacological interference with factors of the loop, we found that inhibition of NAMPT resulted in apoptosis and reduced clonogenic growth in human BRAF-mutant colorectal cancer cell lines and patient-derived tumoroids.
We have used SW48 and LIM1215 human colon cancer cell lines, quadruple wild-type for KRAS, NRAS, BRAF and PI3KCA genes, and their HER2-amplified (LIM1215-HER2 and SW48-HER2) derived cells to perform in vitro and in vivo studies in order to identify novel therapeutic strategies in HER2 gene amplified human colorectal cancer.
The US Food and Drug Administration approved a liquid biopsy test for EGFR-activating mutations in patients with non-small-cell lung cancer as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFR T790M in non-small-cell lung cancer. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAFV600E/V600K in melanoma.
The observed effect of combination trametinib plus chloroquine was not restricted to PDA as other tumors, including patient-derived xenografts (PDX) of NRAS-mutated melanoma and BRAF-mutated colorectal cancer displayed similar responses.
<i>BRAF</i><sup>V600E</sup> mutations occur in ∼10% of colorectal cancer cases, are associated with poor survival, and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition.
Multigene panels identified two previously unreported prognostic associations in colorectal cancer involving TP53 mutation and total mutation burden, and confirmed associations with KRAS and BRAF.
BRAF inhibition-induced Wnt pathway activation was further validated in preclinical models of <i>BRAF</i><sup>V600E</sup>-mutant colorectal cancer, including cell line xenograft model and a patient-derived xenograft model.