• What is MAP2K1?
  • MAP2K1 in Lung Cancer
  • MEK1 c.167A>C (Q56P)
  • 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.167A>C (Q56P) Mutation 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 Q56P mutations in MEK1-mutated NSCLC 19% (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 Q56P mutation results in an amino acid change at position 56 in MEK1, from a glutamine (Q) to a proline (P). This mutation occurs outside of the kinase domain of MEK1 (Figure 1). Preclinical data have shown that this mutation leads to increased MEK1 kinase activity in vitro (Bottorff et al. 1995).

Clinical characteristics of lung cancer patients with tumors harboring Q56P mutations include a strong association with smoking, but no association with age, sex, race or stage (Arcila et al. 2014). Clinical responses of patients harboring a Q56P lung tumor associated mutation to MEK1 inhibitors are unknown at this time​. MEK1 mutations are usually found in tumors wild type for EGFR, ALK, and other driver mutations (Arcila et al. 2014).

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-q56p.png

Figure 1.
Schematic of MEK1 Q56P mutation. Functional domains of MEK1 are depicted. D: Docking domain. NES: Nuclear Export Sequence.

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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.167A>C (Q56P) Mutation in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/map2k1/74/ (Updated January 23).

Last Updated: January 23, 2015

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