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MEK inhibitors under development for treatment of non-small-cell lung cancer

Chul Kim1,2, Giuseppe Giaccone2

  • 1a Thoracic and Gastrointestinal Oncology Branch , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.

Expert Opinion on Investigational Drugs
|December 9, 2017
PubMed
Abstract

Insights

Mitogen-activated protein kinase kinase (MEK) inhibitors show promise for treating non-small-cell lung cancer (NSCLC). Clinical trials are exploring MEK inhibitors alone and in combination therapies for improved patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The mitogen-activated protein kinase (MAPK) pathway is crucial in non-small-cell lung cancer (NSCLC) pathogenesis.
  • Mutations in the MAPK pathway often lead to overactivation of mitogen-activated protein kinase kinase 1/2 (MEK1/2).
  • Targeting MEK1/2 is a rational therapeutic strategy for NSCLC.

Purpose of the Study:

  • To review the biological basis for using MEK inhibitors in NSCLC.
  • To summarize the clinical development and experience with MEK1/2 inhibitors in NSCLC treatment.
  • To discuss current and future therapeutic strategies involving MEK inhibitors.

Main Methods:

  • Review of preclinical data and clinical trial results (Phase I-III).
  • Analysis of MEK inhibitors as monotherapy and in combination regimens.
  • Examination of ongoing research, including combination with immune checkpoint inhibitors.

Main Results:

  • Trametinib plus dabrafenib is approved for BRAF-mutant NSCLC.
  • Several other MEK inhibitors (selumetinib, cobimetinib, binimetinib) are in clinical development.
  • Combination therapies, including with immune checkpoint blockade, are under investigation.

Conclusions:

  • MEK inhibitors represent a significant advancement in NSCLC treatment.
  • Combination strategies and biomarker research are essential for optimizing MEK inhibitor therapy.
  • Further investigation is needed to overcome resistance and improve patient response rates.
Keywords:
BRAFKRASMAPKMEK inhibitornon-small-cell lung cancer

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