BRAF alterations as therapeutic targets in non-small-cell lung cancer

Tu Nguyen-Ngoc, Hasna Bouchaab, Alex A. Adjei, Solange Peters

Research output: Contribution to journalReview articlepeer-review

55 Scopus citations

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 languageEnglish (US)
Pages (from-to)1396-1403
Number of pages8
JournalJournal of Thoracic Oncology
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • BRAF
  • Dabrafenib
  • MEK
  • Non-small-cell lung cancer
  • Trametinib
  • V600E
  • Vemurafenib

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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