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Phase 2 or 3 results paper on KRAS in Colorectal cancer, in Journal of Clinical Oncology (2010), one of the most cited Europe PMC records with KRAS in its title.
Purpose: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting.
Patients and methods: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models.
Results: KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P =.0016), while BRAF mutation was significantly associated with female sex (P =.017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10(-4)). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P =.0003).
Conclusion: In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.
Indexed on Europe PMC as PubMed record 20008640 (DOI 10.1200/jco.2009.23.3452). Its title names KRAS and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea "Covalent chemistry for the RAS mutations that still have no drug" and no figure has been checked by an editor.
One of the most cited trial reports Europe PMC returns for KRAS in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery, Journal of Clinical Oncology.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery, Journal of Clinical Oncology.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.