How Do Antineoplastic MEK Inhibitors Work?

Antineoplastic mitogen-activated protein kinase (MEK) inhibitors are a class of drugs used to treat unresectable or metastatic melanoma (a type of skin cancer) with a BRAF V600E or V600K mutation, neurofibromatosis type 1 (a genetic disorder characterized by the development of multiple noncancerous tumors of nerves and skin [neurofibromas] and areas of abnormal skin color [pigmentation]) in children two years and above, and non-small-cell lung cancer and thyroid cancer.

MEK inhibitors are oral drugs that inhibit the mitogen-activated protein kinase enzymes MEK1 and/or MEK2. MEK enzymes are a part of the MAPK/ERK pathway, which regulates cell proliferation (growth and division) and the biosynthesis of the inflammatory cytokines tumor necrosis factor, interleukin (IL)-6, and IL-1, and these enzymes are overactive in many types of cancers.

The MAPK pathway is an intracellular signaling cascade that is involved in the proliferation and survival of tumor cells. Many mutations cause cancer development by activating this pathway, including BRAF and NRAS mutations.

MEK inhibitors selectively bind to a unique site near the ATP (the principal molecule for storing and transferring energy in cells) binding pocket of the protein kinase that further inhibits the kinase function of this protein by inducing conformational changes that limit the movement of the activation loop by which the kinase is activated. This reduces the rate of Raf-mediated MEK phosphorylation, leaving the enzyme locked in a catalytically inactive state, eventually arresting the signaling pathway.

MEK inhibitors are administered orally twice daily with or without food. 

Antineoplastic MEK inhibitors are used to treat conditions such as:

• Melanoma (a type of skin cancer)
• Non-small cell lung cancer
• Thyroid cancer
• Neurofibromatosis type 1 (a genetic disorder characterized by the development of multiple noncancerous tumors of nerves and skin [neurofibromas] and areas of abnormal skin color [pigmentation])

Some of the common side effects include:

• Nausea
• Vomiting
• Constipation
• Diarrhea
• Headache
• Tiredness/weakness
• Mouth ulcers
• Loss of appetite
• Abdominal pain
• Dry skin
• Altered taste sensation

Other rare side effects include:

• Dizziness 
• Fatigue 
• Weight loss
• Hair loss
• Blurred vision
• Anemia (low red blood cell count)
• Shortness of breath
• Chills, sore throat, fever, or cough
• Rash/hives/itching
• Thrombocytopenia (low blood platelet count)
• Hypertension (high blood pressure)
• Hypocalcemia (low blood calcium level)
• Painful, frequent, burning, or difficult urination
• Peripheral edema (swelling of lower legs or hands)
• Increased creatinine (a waste product formed by the normal breakdown of muscle cells)
• Yellow eyes or skin
• Paronychia (skin infection around the fingernails or toenails)
• Epistaxis (bleeding from the nose)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of antineoplastic MEK inhibitors include:

• Binimetinib
• Cobimetinib
• Cotellic
• Koselugo
• Mekinist
• Mektovi
• Selumetinib
• Trametinib