MEK inhibitor

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A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical significance.)

Hence MEK inhibitors have potential for treatment of some cancers,[1] especially BRAF-mutated melanoma,[2] and KRAS/BRAF mutated colorectal cancer.[3]

Approved for clinical use[edit]

  • Trametinib (GSK1120212), FDA-approved to treat BRAF-mutated melanoma. Also studied in combination with BRAF inhibitor dabrafenib to treat BRAF-mutated melanoma.
  • Cobimetinib or XL518, approved by US FDA in Nov 2015 for use in combination with vemurafenib (Zelboraf(R)), for treatment of advanced melanoma with a BRAF V600E or V600K mutation.

In clinical trials[edit]

  • Binimetinib (MEK162), is currently in phase 3 clinical trials for ovarian cancer,[4] BRAF mutant melanoma,[5] and NRAS mutant melanoma.[6]
  • Selumetinib, had a phase 2 clinical trial for non-small cell lung cancer (NSCLC) which demonstrated an improvement in PFS,[7] and is now in phase III development in KRAS mutation positive NSCLC (SELECT-1, NCT01933932). Other ph 3 clinical trials underway include uveal melanoma (failed), and differentiated thyroid carcinoma.
  • PD-325901, for breast cancer, colon cancer, and melanoma[8] A phase II trial for advanced non-small cell lung cancer "did not meet its primary efficacy end point".[9]



  1. ^ Wang, Ding; Boerner, Scott A.; Winkler, James D.; Lorusso, Patricia M. (2007). "Clinical experience of MEK inhibitors in cancer therapy". Biochim Biophys Acta. 1773 (8): 1248–55. PMID 17194493. doi:10.1016/j.bbamcr.2006.11.009. 
  2. ^ "ASCO: MEK Inhibitors—Alone or Paired With a BRAF Inhibitor—Increase Options, Benefits for Patients With BRAF-Mutated Advanced Melanoma". 2012. 
  3. ^ KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. 2009
  4. ^ A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer
  5. ^ Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma (COLUMBUS)
  6. ^ Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
  7. ^ Jänne, Pasi A; Shaw, Alice T; Pereira, José Rodrigues; Jeannin, Gaëlle; Vansteenkiste, Johan; Barrios, Carlos; Franke, Fabio Andre; Grinsted, Lynda; Zazulina, Victoria; Smith, Paul; Smith, Ian; Crinò, Lucio (2013). "Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: A randomised, multicentre, placebo-controlled, phase 2 study". The Lancet Oncology. 14 (1): 38–47. PMID 23200175. doi:10.1016/S1470-2045(12)70489-8. 
  8. ^ MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma
  9. ^ Haura EB, Ricart AD, Larson TG, Stella PJ, Bazhenova L, Miller VA, Cohen RB, Eisenberg PD, Selaru P, Wilner KD, Gadgeel SM. "A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer". Clin Cancer Res. 16: 2450–7. PMID 20332327. doi:10.1158/1078-0432.CCR-09-1920. 
  10. ^ MEK inhibitor, TAK-733 reduces proliferation, affects cell cycle and apoptosis, and synergizes with other targeted therapies in multiple myeloma. Feb 2016