Trametinib, sold under the brand name Mekinist among others, is an anticancer medication used for the treatment of

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

. It is a

MEK inhibitor 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 sign ...

drug with anti-cancer activity. It inhibits

MEK1 Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the ''MAP2K1'' gene. Function The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mito ...

and

MEK2 Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the ''MAP2K2'' gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2. Function The ...

. Trametinib had good results for metastatic

carrying the BRAF

V600E V600E is a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600. It is a driver mutation in a proportion of certain diagnoses, including melanoma, hairy cell leukemia, papillary thyroid carcinoma, col ...

mutation in a phase III clinical trial. In this mutation, the amino acid

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotona ...

(V) at position 600 within the BRAF protein has become replaced by

glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

(E) making the mutant BRAF protein constitutively active. In May 2013, trametinib was approved as a single-agent by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

for the treatment of people with V600E mutated metastatic melanoma. Clinical trial data demonstrated that resistance to single-agent trametinib often occurs within 6 to 7 months. To overcome this, trametinib was combined with the BRAF inhibitor

dabrafenib Dabrafenib, sold under the brand name Tafinlar & Rafinlar ( both by Novartis) among others, is a medication for the treatment of cancers associated with a mutated version of the gene BRAF. Dabrafenib acts as an inhibitor of the associated enzyme ...

. As a result of this research, on January 8, 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma. On May 1, 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after

surgical resection Segmental resection (or segmentectomy) is a surgical procedure to remove part of an organ or gland, as a sub-type of a resection, which might involve removing the whole body part. It may also be used to remove a tumor and normal tissue around it ...

based on the results of the COMBI-AD phase 3 study, making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.

Other uses

In a person with a sequence variant in the ''

ARAF Serine/threonine-protein kinase A-Raf or simply A-Raf is an enzyme that in humans is encoded by the ''ARAF'' gene. A-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases. Compared to the other members of this ...

'' gene, trametinib helped the

lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid ...

to remodel toward a healthier state, reducing lymphatic edema. This benefit would not occur in most people because it is specific to genomes similar to the reported one, but it is potentially lifesaving for the few people with such genomes. This case provides an example of what

precision medicine Precision, precise or precisely may refer to: Science, and technology, and mathematics Mathematics and computing (general) * Accuracy and precision, measurement deviation from true value and its scatter * Significant figures, the number of digi ...

can accomplish.

References

External links

* Cancer treatments Cyclopropyl compounds Fluoroarenes Iodoarenes Acetanilides MEK inhibitors GSK plc brands Novartis brands {{antineoplastic-drug-stub