How Do Antineoplastic BRAF Kinase Inhibitor Work?

Antineoplastic BRAF inhibitors are a class of drugs used to treat melanoma with BRAF V600E mutation (a type of skin cancer) that cannot be treated with surgery or has spread to other parts of the body. They are also used to treat thyroid, colorectal, and lung cancers and Erdheim-Chester disease (a disease that causes an overproduction of a type of white blood cells).

BRAF (a human gene that encodes a protein called B-Raf) mutations occur in 50% of melanomas. BRAF inhibitors are kinase enzymes that target the mutant BRAF and inhibit the over-activated MAPK signaling pathway, which mediates cell growth and survival, thus causing a reduction in tumor cell proliferation.

BRAF kinase inhibitors are administered via intravenous (into the vein) and oral routes. 

BRAF kinase inhibitors work in the following ways:

• They belong to a class of drugs called "kinase inhibitors" that work by slowing down or stopping the growth of cancer cells.
• They block the action of an abnormal protein (mutant B-Raf, which is mutated in approximately 50% of patients with melanoma) that signals cancer cells to multiply.
• B-Raf is a protein and a part of the cell signaling pathway that controls cell growth in different tissues in the body.

Mutations that lock the B-Raf protein in an active state can cause excessive signaling in the RAS/RAF/MEK/ERK (MAPK pathway) signaling pathway, leading to uncontrolled growth of melanocytes (pigment cells).

BRAF inhibitors block the activity of mutant B-Raf preventing the growth of cancer cells and eventually causing its death.

Antineoplastic BRAF kinase inhibitors are used to treat conditions such as:

• Malignant melanoma
• Metastatic colorectal cancer
• Non-small cell lung cancer
• Thyroid cancer
• Erdheim-Chester disease (a rare type of slow-growing blood cancer called a histiocytic neoplasm, which results in overproduction of cells called histiocytes that normally function to destroy foreign substances and protect the body from infection)

Some of the common side effects include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Tiredness/weakness
• Bone/joint/muscle pain
• Dry/itchy skin
• Constipation
• Decreased appetite

Other rare side effects include:

• Dizziness 
• Fatigue 
• Temporary hair loss
• Blurry vision
• Rash
• Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• Changes in skin (new wart, skin sore, or red bump that bleeds or does not heal)
• Fast, irregular, or pounding heartbeat
• Hypertension (high blood pressure)
• Shortness of breath
• Chest pain
• Hyperglycemia (high blood glucose levels)
• Actinic keratosis (a pre-cancerous area of thick, scaly, or crusty skin)
• Chills, sore throat, fever, or cough

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 BRAF kinase inhibitors include:

• Braftovi
• Dabrafenib
• Encorafenib
• Tafinlar
• Vemurafenib
• Zelboraf