Trametinib, sold under the brand name Mekinist among others, is an
anticancer medication
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
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
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 ( ...
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, ...
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 deprotonat ...
(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 List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
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 enzym ...
.
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 In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to:
* Adjuvant therapy in cancer management
* Analgesi ...
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 i ...
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 o ...
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 digit ...
can accomplish.
References
External links
*
Cancer treatments
Cyclopropyl compounds
Fluoroarenes
Iodoarenes
Acetanilides
MEK inhibitors
GSK plc brands
Novartis brands
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