Project description:Metastatic colorectal carcinoma is one of the most common cancers in the world, second most commonly diagnosed cancer in Europe. Approximately 25% of patients initially diagnosed with colorectal carcinoma have metastases at the time of the first diagnosis and almost 50% of the diagnosed patients develop metastases, which explains the high mortality rate of these tumors. The carcinogenic process can be inhibited by the inactivation of EGFR receptors, making them important therapeutic targets. However, around 90-80% of patients do not respond to the EGFR targeted therapy. Resistance is mainly due to KRAS gene mutations. In this study, we built a 171 mutations panel (OncoAlvo®) that screens all mutations recommended by the ESMO, ASCO & NICE Medical Guidelines with 99% accuracy. The samples were simultaneously genotyped by other techniques to validate our panel and accuracy.

2018-10-26 | GSE121805 | GEO

Genomics characterization of BRAF-V600E colorectal cancer patients treated with anti-BRAF/EGFR

Project description:Anti-BRAF/EGFR combinatorial therapy was recently approved by the FDA and EMA for the treatment of metastatic BRAF-V600E colorectal cancer (CRCBRAF-V600E), however the underlying genetic determinants of its anti-tumoral efficacy remain unknown. Using whole-exome sequencing data in an internal cohort of CRCBRAF-V600E treated with anti-BRAF/EGFR Ã‚Â± combinatorial therapies, we discovered that patients with MSS-RNF43mutated tumors achieved a higher ORR in comparison with MSI-RNF43mutated and MSS-RNF43wild-type. Multivariate analysis of an external validation cohort showed improved PFS and OS of MSS-RNF43mutated in comparison with MSS-RNF43wild-type. In vitro assessment of RNF43 mutations identified in MSS tumors showed a loss-of-function effect. Overall, our findings support a crucial role of the RNF43-dependent modulation of the WNT pathway in the antitumor activity of anti-BRAF/EGFR Ã‚Â± combinatorial therapies and may guide patient stratification strategies for future clinical studies.

| EGAS00001006247 | EGA

Ramucirumab plus FOLFIRI as second-line treatment for patients with RAS wild-type metastatic colorectal cancer previously treated with anti-EGFR antibody: JACCRO CC-16.

Project description: Not available

| S-EPMC10594013 | biostudies-literature

Association of Anti-EGFR Antibody and MEK Inhibitor in Gynecological Cancer Harboring RAS Mutation: A Case Series.

Project description: Not available

| S-EPMC8948991 | biostudies-literature

Acquired Secondary RAS Mutation in BRAF<sup>V600E</sup>-Mutated Thyroid Cancer Patients Treated with BRAF Inhibitors.

Project description: Not available

| S-EPMC7869871 | biostudies-literature