Targeting of MEK in lung cancer therapeutics

David F Heigener; David R Gandara; Martin Reck

doi:10.1016/S2213-2600(15)00026-0

Targeting of MEK in lung cancer therapeutics

Lancet Respir Med. 2015 Apr;3(4):319-27. doi: 10.1016/S2213-2600(15)00026-0. Epub 2015 Mar 20.

Authors

David F Heigener¹, David R Gandara², Martin Reck³

Affiliations

¹ Department of Thoracic Oncology, LungenClinic Grosshansdorf; member of the Airway research center north (ARCN) as part of the German Centre for Lung Research (DZL), Grosshansdorf, Germany. Electronic address: dheigener@aol.com.
² Division of Hematology/Oncology, UC Davis Comprehensive Cancer Center, Sacramento, USA.
³ Department of Thoracic Oncology, LungenClinic Grosshansdorf; member of the Airway research center north (ARCN) as part of the German Centre for Lung Research (DZL), Grosshansdorf, Germany.

PMID: 25801412
DOI: 10.1016/S2213-2600(15)00026-0

Abstract

The MAP-kinase pathway, consisting of the kinases RAS, RAF, MEK, and ERK, is crucial for cell proliferation, inhibition of apoptosis, and migration of cells. Direct inhibition of RAS is not yet possible, whereas inhibition of RAF is already established in malignant melanoma and under investigation in non-small-cell lung cancer (NSCLC). Due to their structure and function, the MEK proteins are attractive targets for cancer therapy and are also under investigation in NSCLC. We discuss strategies of targeting the RAS-RAF-MEK-ERK pathway with emphasis on MEK inhibition, either alone or in combination with other targets or conventional chemotherapy.

Publication types

Review

MeSH terms

Benzimidazoles / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / metabolism
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / metabolism
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / metabolism
Molecular Targeted Therapy
Protein Kinase Inhibitors / therapeutic use*
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins B-raf / metabolism
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / metabolism
Pyridones / therapeutic use*
Pyrimidinones / therapeutic use*

Substances

AZD 6244
Benzimidazoles
KRAS protein, human
Protein Kinase Inhibitors
Pyridones
Pyrimidinones
trametinib
BRAF protein, human
Proto-Oncogene Proteins B-raf
Extracellular Signal-Regulated MAP Kinases
Proto-Oncogene Proteins p21(ras)