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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
How far we have come targeting BRAF-mutant non-small cell lung cancer (NSCLC)
Fabrizio Tabbò1, Chiara Pisano1, Julien Mazieres2
1Department of Oncology, San Luigi Hospital, University of Torino, Orbassano (TO), Italy.
Abstract:
The advent of high-throughput sequencing has allowed to profoundly interrogate the molecular landscape of non-small cell lung cancer (NSCLC) in the last years. These findings constitute the opportunity to better stratify these patients in order to address specific treatments to well-defined oncogene-restricted subgroups. Among them, BRAF-mutated lung cancers represent around 4% of NSCLC, thus identifying a clinically relevant population that should be aptly managed. Pivotal phase II trials have demonstrated the efficacy of combinatorial treatment - dabrafenib plus trametinib, targeting both BRAF and MEK - for patients harboring V600E mutations, making this specific BRAF alteration a mandatory requirement in the genetic portrait of advanced non-squamous lung cancer patients. However, around half of BRAF+ NSCLC patients remain orphan of targeted approaches. Here we review the available evidence, mainly from a clinical perspective, of therapeutic strategies for both V600E and non-V600 patients, in terms of small molecule, immune checkpoint inhibitors and forthcoming integrated strategies. Looking at on-going clinical trials, a special attention is dedicated to emergent molecules and combinatorial strategies that not only will improve outcomes of classical V600E, but also will make concrete the chance of tailored treatments for the majority of BRAF-mutated patients.
Insights
High-throughput sequencing reveals BRAF mutations in non-small cell lung cancer (NSCLC). Targeted therapies like dabrafenib plus trametinib show promise for V600E mutations, with ongoing research for other BRAF alterations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- High-throughput sequencing has advanced the understanding of non-small cell lung cancer (NSCLC) molecular profiles.
- BRAF mutations occur in approximately 4% of NSCLC cases, identifying a targetable patient subgroup.
- Current targeted therapies primarily benefit patients with BRAF V600E mutations.
Purpose of the Study:
- To review current and emerging therapeutic strategies for BRAF-mutated NSCLC.
- To discuss treatment options for both V600E and non-V600 BRAF alterations.
- To highlight ongoing clinical trials and future treatment directions.
Main Methods:
- Review of clinical evidence and ongoing clinical trials.
- Focus on small molecule inhibitors, immune checkpoint inhibitors, and integrated strategies.
- Analysis from a clinical perspective.
Main Results:
- Combinatorial treatment (dabrafenib plus trametinib) is effective for BRAF V600E-mutated NSCLC.
- A significant proportion of BRAF-mutated NSCLC patients currently lack targeted treatment options.
- Emerging molecules and combinatorial strategies aim to expand treatment access for diverse BRAF alterations.
Conclusions:
- BRAF mutation status is crucial for stratifying NSCLC patients for targeted therapy.
- While V600E mutations have established treatments, non-V600 mutations require further therapeutic development.
- Future strategies promise tailored treatments for a broader range of BRAF-mutated NSCLC patients.
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