Technical advance in targeted NGS analysis enables identification of lung cancer risk-associated low frequency TP53, PIK3CA, and BRAF mutations in airway epithelial cells.
BRAF- and MEK-targeted therapies are effective in BRAFV600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance.
This interesting phenomenon (often called "drug dependency" or "drug addiction") is exemplified in preclinical acquired resistance models of BRAF-mutated melanoma treated with vemurafenib and EGFR-mutated lung cancer treated with EGFR tyrosine kinase inhibitors.
Our clinical data suggest that BRAF mutations define specific subsets of patients with NSCLC; while their oncogenic nature is yet to be established in lung cancer, especially for non-V600E mutations, the value of BRAF mutations to predict the efficacy of targeted agents remains unclear.
Combined genomic and proteomic analyses demonstrated infrequent alteration of validated lung cancer targets (including the absence of BRAF mutations in TTF1-negative LUAD), but identified novel potential targets for TTF1-negative LUAD, including KEAP1/Nrf2 and DNA repair pathways.
Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens.
BRAFV600E is an emerging drug target in lung cancer, but the clinical significance of non-V600 BRAF mutations in lung cancer and other malignancies is less clear.
We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers.
These data, together with the nonoverlapping pattern of EGFR and BRAF mutations in human lung cancer, suggest that these lesions define distinct clinical entities whose treatment should be guided by prospective real-time genotyping.
In this study, using both novel and established technologies, we developed a clinically practical assay to survey the status of three frequently mutated genes in lung cancer (EGFR, K-ras and TP53) and two genes (BRAF and β-catenin) with known hotspot mutations in many other cancers.