• What is MAP2K1?
  • MAP2K1 in Lung Cancer
  • MEK1 c.171G>T (K57N)
  • Clinical Trials

MEK1 (MAP2K1)

MEK1 (also known as MAP2K1) is a serine-threonine protein kinase that is a central mediator in the MAP kinase signaling pathway. As part of the MAP kinase pathway, MEK1 is involved in many cellular processes, including cell proliferation, differentiation, and transcriptional regulation.

mapk-pk13.png

Figure 1.
Schematic of the MAPK and PI3K pathways. Growth factor binding to receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. MEK1 (MAP2K1). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/map2k1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

MEK1 (MAP2K1) in Non-Small Cell Lung Cancer (NSCLC)

Somatic mutations in MEK1 (MAP2K1) have been found in approximately 1% of all NSCLC and are more common in adenocarcinoma than squamous cell carcinoma (Arcila et al. 2014; Marks et al. 2008). In a retrospective study of 36 MEK1-mutated lung adenocarcinoma patient cases, MEK1 mutations were more prevalent in tumors from smokers or former smokers, and there were no other associations with age, sex, race or stage (Arcila et al. 2014). In this series, the most frequently observed mutations were K57N (64%) and Q56P (19%), and MEK1 mutations were mutually exclusive with mutations in EGFR, KRAS, BRAF and other driver mutations (Arcila et al. 2014).

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. MEK1 (MAP2K1) in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/map2k1/ (Updated June 18).

Last Updated: June 18, 2015

MEK1 (MAP2K1) c.171G>T (K57N) Mutations in Non-Small Cell Lung Cancer (NSCLC)

Properties
Location of mutation Exon 2
Frequency of MEK1 mutations in NSCLC ~1% (Marks et al. 2008)
Frequency of K57N mutations in MEK1-mutated NSCLC 64% (Arcila et al. 2014)
Implications for Targeted Therapeutics
Response to MEK inhibitors Unknown at this time
Response to EGFR TKIs Unknown at this timea
Response to anti-EGFR antibodies Unknown​ at this time​

The K57N mutation results in an amino acid change at position 57 in MEK1, from a lysine (K) to an asparagine (N). This mutation occurs outside of the kinase domain of MEK1 (Figure 1). Preclinical data have shown that this mutation leads to constitutive activation of the MAPK signaling pathway in vitro (Marks et al. 2008).

Clinical characteristics of lung cancer patients with tumors harboring K57N mutations include a strong association with smoking, but no association with age, sex, race or stage (Arcila et al. 2014). In vitro studies suggest that the K57N mutation is sensitive to a MEK1 small molecule non-ATP competitive inhibitor (AZD6244; Marks et al. 2008).

a The presence of MEK1 mutations has been associated with in vitro resistance to EGFR TKIs (Marks et al. 2008). However, it should be noted that MEK1 mutations are usually found in tumors wild type for EGFR, ALK, and other driver mutations.

mek1-k57n.png

Figure 1.
Schematic of MEK1 K57N mutation. Functional domains of MEK1 are depicted. D: Docking domain. NES: Nuclear Export Sequence.

​​​

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. MEK1 (MAP2K1) c.171G>T (K57N) Mutations in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/map2k1/72/ (Updated January 23).

Last Updated: January 23, 2015

My Cancer Genome has released its new and improved cancer clinical trials search tool on our beta website. Please visit beta.padiracinnovation.org to check it out!

Disclaimer: The information presented at padiracinnovation.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.