Selumetinib in the treatment of non-small-cell lung cancer

Future Oncol. 2016 Nov;12(22):2545-2560. doi: 10.2217/fon-2016-0132. Epub 2016 Jul 28.


The RAS-RAF-MEK-ERK pathway regulates processes involved in the proliferation and survival of cells. KRAS mutations, prevalent in approximately 30% of patients with non-small-cell lung cancer (NSCLC), result in constitutive activation of the pathway. Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. Several trials in combination with other chemotherapy and targeted therapy regimens in lung cancer are ongoing. We review the development of selumetinib in patients with NSCLC, summarize the pharmacodynamic, pharmacokinetic and tolerability characteristics, and the available clinical trial data to understand the role of selumetinib in the treatment of NSCLC.

Keywords: MEK inhibitor; non-small-cell lung cancer; selumetinib.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Docetaxel
  • Humans
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • MAP Kinase Kinase 2 / antagonists & inhibitors
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Taxoids / therapeutic use


  • AZD 6244
  • Benzimidazoles
  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Taxoids
  • Docetaxel
  • MAP2K2 protein, human
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • MAP2K1 protein, human
  • Proto-Oncogene Proteins p21(ras)