EGFR+ (del 19, L858R, G719X, S768I, L851Q) NSCLC clinical samples (formalin-fixed paraffin-embedded tumor and blood) were analyzed for the presence of receptor tyrosine kinase (RTK) and BRAF fusions.
Due to the rarity of BRAFV600E mutation, no randomized study has compared the combination targeted therapy dabrafenib + trametinib with other second-line treatments for advanced or metastatic non-small-cell lung cancer (NSCLC).
Patients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS).
Whilst cytotoxic chemotherapy has been the backbone of advanced non-small cell lung cancer (NSCLC) treatment for decades, the development of targeted agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the treatment paradigm and natural history of this disease.
In the present review, we propose an overview of the available evidence about BRAF in NSCLC mutations (V600E and non-V600E), from biological significance to emerging clinical implications of BRAF mutations detection.
In total 50 plasma samples from patients newly diagnosed with advanced NSCLC or resistant to first-line tyrosine kinase inhibitors (TKIs) were subjected to deep sequencing on a seven-gene panel (BRAF, EGFR, ERBB2, KRAS, NRAS, PIK3CA, PTEN) incorporated with molecular barcodes to improve accuracy in variant detection.
The US FDA approved a liquid biopsy test for EGFR activating mutations in patients with non-small cell lung cancer (NSCLC) as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFR T790M in NSCLC. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAFV600E/V600K in melanoma.
Here we demonstrated that a combination of MEK and BRAF inhibitors overcomes paradoxical MAPK activation (induced by BRAF inhibitors) in BRAF-wt/RAS-mut NSCLC and PDAC in vitro.
There was a significant association between BRAF mutations and adenocarcinomas (ADCs) in NSCLC compared with non-ADCs (OR = 3.96, 95% CI = 2.13-7.34, P < 0.0001).
In this review we discuss the latest evidence on the treatment of BRAF-mutated NSCLC, including tumor biology, targeted treatment with BRAF and MEK inhibitors, therapeutic resistance and strategies to overcome resistance.
Direct inhibition of mutant B-Raf proto-oncogene, serine/threonine kinase (BRAF) and/or downstream mitogen-activated protein kinase kinase (MEK) has the potential to change the course of the disease for patients with <i>BRAF</i>-mutant NSCLC, as it has in <i>BRAF</i>-mutant melanoma.
In this study, we assessed 179 clinical cases of non-small cell lung carcinoma (NSCLC) that had been previously tested for EGFR, KRAS, NRAS, and BRAF mutations using a novel multiplexed analytic approach that reduces wild-type signal and allows for detection of low mutation load approaching 1%, iPLEX® HS panel for the MassARRAY® System (Agena Bioscience, San Diego, CA).
Herein, beyond describing a cohort of BRAF mutant NSCLC patients and functionally analyzing 13 tumor-derived BRAF mutations, we demonstrate that both types of non-V600 BRAF mutations can be sensitive to clinically relevant doses of Dabrafenib and Trametinib in HEK293T cells, in lung epithelial cellular model (BEAS-2B) and in human cancer cell lines harboring non-V600 BRAF mutations.
In this review, we will cover the role of targeted therapies for NSCLC harbouring BRAF, MET, HER2 and RET alterations, all of which have shown promise in non-squamous non-small cell lung cancer (ns-NSCLC).
Combined BRAF and EGFR inhibition blocked reactivation of ERK signaling and improved efficacy in vitro and in vivo Our findings support the evaluation of combined BRAF and EGFR inhibition in NSCLC(V600E) with acquired resistance to BRAF inhibitors.
In this phase 2, multicentre, non-randomised, open-label study, we enrolled adult patients (aged ≥18 years) with pretreated metastatic stage IV BRAF(V600E)-mutant NSCLC who had documented tumour progression after at least one previous platinum-based chemotherapy and had had no more than three previous systemic anticancer therapies.