Abstract
Background: Several subsets of non-small-cell lung cancer (NSCLC) are defined by molecular alterations acting as tumor drivers, some of them being currently therapeutically actionable. The rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway constitutes an attractive potential target, as v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations occur in 2-4% of NSCLC adenocarcinoma. Methods: Here, we review the latest clinical data on BRAF serine/threonine kinase inhibitors in NSCLC. Results: Treatment of V600E BRAF-mutated NSCLC with BRAF inhibitor monotherapy demonstrated encouraging antitumor activity. Combination of BRAF and MEK inhibitors using dabrafenib and trametinib is under evaluation. Preliminary data suggest superior effi-cacy compared with BRAF inhibitor monotherapy. Conclusion: Targeting BRAF alterations represents a promising new therapeutic approach for a restricted subset of oncogene-addicted NSCLC. Prospect ive trials refining this strategy are ongoing. A next step will probably aim at combining BRAF inhibitors and immunotherapy or alternatively improve a multilevel mitogen-activated protein kinase (MAPK) pathway blockade by combining with ERK inhibitors.
Original language | English (US) |
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Pages (from-to) | 1396-1403 |
Number of pages | 8 |
Journal | Journal of Thoracic Oncology |
Volume | 10 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2015 |
Keywords
- BRAF
- Dabrafenib
- MEK
- Non-small-cell lung cancer
- Trametinib
- V600E
- Vemurafenib
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine