Overall, the current study has identified activation of the Wnt/β-catenin pathway as a novel fundamental cause of colon cancer resistance to BRAF inhibition.
Among patients with non-MSI-high cancer, BRAF mutation status emerged as a distinct marker with higher connectivity in the network of proximal colon cancer, but not in distal colorectal cancer.
The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis.
To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions.
These findings illustrate the utility of non-invasive PET imaging measures of glutamine uptake to selectively predict response to BRAF-targeted therapy in colon cancer and may suggest further opportunities to inform colon cancer clinical trials using targeted therapies against MAPK activation.
Activating BRAF mutations promote constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway and are common in a variety of human malignancies, including melanoma and colon cancer.
Complex <b>1</b> has an outstanding inhibitory effect against BRAF-mutant colon carcinoma and hepatocarcinoma cell growth; <b>1</b> and <b>2</b> are both more active than the free ligand and have the capacity to trigger early apoptotic processes.
Comparison of the transcriptome data of metastasis-competent CTC-MCC-41 cells and of HT-29 cells (derived from a primary colon cancer) highlights the differential expression of genes that regulate energy metabolism [peroxisome proliferator-activated receptor γ coactivator 1A (<i>PPARGC1A</i>), peroxisome proliferator-activated receptor γ coactivator 1B (<i>PPARGC1B</i>), fatty acid binding protein 1 (<i>FABP1</i>), aldehyde dehydrogenase 3 family member A1 (<i>ALDH3A1</i>)], DNA repair [BRCA1 interacting protein C-terminal helicase 1 (<i>BRIP1</i>), Fanconi anemia complementation group B (<i>FANCB</i>), Fanconi anemia complementation group M (<i>FANCM</i>)], and stemness [glutaminase 2 (<i>GLS2</i>), cystathionine-beta-synthase (<i>CBS</i>), and cystathionine gamma-lyase (<i>CTH</i>)].
Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer.
The mutational status of KRAS and BRAF(V600E) oncogenes combined with analysis of the DNA mismatch repair system with/without the CpG island methylator phenotype (CIMP) has been shown to identify colon cancer subtypes with distinct clinical features and prognoses.
Here we report that colon cancer cells with mutant BRAF are also resistant to the heat shock protein 90 (HSP90) inhibitor AUY922, and that this is caused by rebound activation of ERK and Akt.
Transient exposure to CDDP and induction of the CDDP resistance decreased expression of peroxisome proliferator-activated receptor-γ (PPARγ) in MKN45 and colon cancer LoVo cells.
We also correlated EZR and PPARγ expression in our series of CRC specimens and the expression profiling of all five proteins levels in the publicly available colon cancer genomic data from Oncomine and Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) datasets.
Effect of MTH1 inhibition on tumour growth was explored in BRAFV600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models.
BRAF (V600E) and KRAS mutations were analyzed in node-positive colon cancer patients (n = 3305) treated with FOLFOX-based chemotherapy in an adjuvant trial (Alliance N0147).
Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study.