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.)
Approved for clinical use
- 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.
- Binimetinib (MEK162), approved by the FDA in June 2018 in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.
In clinical trials
- Selumetinib, had a phase 2 clinical trial for non-small cell lung cancer (NSCLC) which demonstrated an improvement in PFS, 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 A phase II trial for advanced non-small cell lung cancer "did not meet its primary efficacy end point".
- 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. doi:10.1016/j.bbamcr.2006.11.009. PMID 17194493.
- "ASCO: MEK Inhibitors—Alone or Paired With a BRAF Inhibitor—Increase Options, Benefits for Patients With BRAF-Mutated Advanced Melanoma". 2012.
- KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. 2009
- Research, Center for Drug Evaluation and. "Approved Drugs - FDA approves encorafenib and binimetinib in combination for unresectable or metastatic melanoma with BRAF mutations". www.fda.gov. Retrieved 2018-07-17.
- 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. doi:10.1016/S1470-2045(12)70489-8. PMID 23200175.
- MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma
- 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. doi:10.1158/1078-0432.CCR-09-1920. PMID 20332327.
- MEK inhibitor, TAK-733 reduces proliferation, affects cell cycle and apoptosis, and synergizes with other targeted therapies in multiple myeloma. Feb 2016