Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC.
We found that the human colorectal cancer cell line, HCT-116, displayed reduced expression of Raf1-tr, and reintroduction of Raf1-tr sensitized the cells to bleomycin-induced apoptosis.
The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations.
Tumour budding is associated with the mesenchymal colon cancer subtype and RAS/RAF mutations: a study of 1320 colorectal cancers with Consensus Molecular Subgroup (CMS) data.
MEK (mitogen-activated protein kinase kinase-MAPKK) 1/2 is a transducer of the growth factor receptor-RAS-RAF-MAPK signalling cascade and plays a relevant role in development and progression of human cancers, such as colorectal cancer (CRC), non small cell lung cancer (NSCLC).
The anti-proliferative effects of LY3009120 in KRASmut CRC cell lines phenocopied molecular inhibition of RAF isoforms by simultaneous siRNA-mediated knockdown of ARAF, BRAF and CRAF.
Concurrent EGFR and RAF inhibition demonstrated synergistic antitumor activity for colorectal cancer PDX models with a <i>KRAS</i> or <i>BRAF</i> mutation.<i></i>.
Overall, our results show that mechanisms of resistance converge on formation of RAF dimers and that inhibiting EGFR and RAF dimers can effectively suppress ERK-driven growth of resistant colorectal cancer.<i></i>.
The available clinical results suggest that while the use of unselective RAF inhibitors (e.g., sorafenib) has been ineffective in the management of advanced CRC patients with KRAS mutation, combination of selective BRAF inhibitors plus EGFR inhibitors may represent a good therapeutic strategy in BRAF-mutant CRC.
KRAS mutations have a significant role in the consecutive activation of RAS.RAF.MEK.ERK pathway in colorectal cancer.Approximately 30.35% of sporadic colorectal cancers have KRAS mutation.
We analyzed the mutation spectra of the PI3K/PTEN/AKT and RAS/RAF/MAPK pathways in colorectal cancers and the associations of these mutations with sites of metastases or recurrence.
These results demonstrate that AKT1 E17K mutation in advanced colorectal carcinoma is associated with mucinous morphology, PIK3CA wild-type status, and concurrent RAS/RAF mutations with similar pattern to PIK3CA exon 21 mutants.
To gain additional insights into this difference, we performed a genome-scale pooled shRNA enhancer screen in a BRAF-mutant, RAF inhibitor-resistant colorectal cancer cell line exposed to the selective RAF inhibitor PLX4720.
Gain of ALK gene copy number may predict lack of benefit from anti-EGFR treatment in patients with advanced colorectal cancer and RAS-RAF-PI3KCA wild-type status.
The added predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment.
Small interfering RNA (siRNA) screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition.