Trametinib in the treatment of multiple malignancies harboring MEK1 mutations.

Trametinib in the treatment of multiple malignancies harboring MEK1 mutations.

Publication date: Dec 01, 2019

The aberrant activation of RAS-derived mitogen-activated protein kinase (MAPK) signaling pathway plays a prominent role in tumorigenesis of an array of malignancies. The reasons are usually the upstream activated mutations including mitogen-activated protein kinase kinase 1/2 (MEK1/2). As oncogenic mutations, MEK1 mutations have been observed in a variety of malignancies including melanoma, histiocytic neoplasms, colorectal cancer and lung cancer. Presently, the use of trametinib, a highly selective MEK1/2 inhibitor, was limited to BRAF mutations, according to the approvals of FDA. Therefore, we consider that this is a question worth studying that whether malignancies with MEK1 mutations are sensitive to the treatment of trametinib. This review discussed the function of MEK1 mutations, retrieved the frequency and distribution of MEK1 mutations in various malignancies, and reviewed the basic experiments and clinical case reports on trametinib in the treatment of cell lines or patients with MEK1 mutations. Most studies have demonstrated that trametinib was effective to cells or tumor patients harboring MEK1 mutations, which suggest that the MEK1 mutations might be potential indications of trametinib therapy. In addition, it was also reported that resistance was observed in the treatment of trametinib, suggesting that different MEK1 mutations may have different response to trametinib, and further studies are necessary to distinguish that which MEK1 mutations are appropriate for the treatment with trametinib and which are not.

Lian, T., Li, C., and Wang, H. Trametinib in the treatment of multiple malignancies harboring MEK1 mutations. 24992. 2019 Cancer Treat Rev (81):

Concepts Keywords
FDA MAPK/ERK pathway
Frequency MAP2K1
Histiocytic Trametinib
Inhibitor Cancer treatments
Kinase Acetanilides
Lung Cancer Oncogenes
Malignancies Protein kinases
Melanoma Signal transduction
Mitogen Branches of biology
Neoplasms Enzymes
Oncogenic Trametinib effective tumor
RAS Melanoma


Type Source Name
pathway KEGG MAPK signaling pathway
disease MESH lung cancer
pathway KEGG Melanoma
disease MESH melanoma
disease MESH tumorigenesis
drug DRUGBANK Rasagiline
disease MESH malignancies
disease MESH multiple
drug DRUGBANK Trametinib


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