What are BRAF and MEK inhibitors?
What are BRAF and MEK inhibitors?
BRAF and MEK inhibitors block the activity of the V600E and V600K mutations respectively (2-6) and the combination of a BRAF and MEK Inhibitor is standard treatment for individuals with advanced melanoma and these cancer driving mutations.
Why are BRAF and MEK inhibitors used together?
In comparison with single agent BRAF inhibitors, the combination of BRAF and MEK inhibitors have shown significant improvement in response rates, PFS and OS in addition to fewer side effects related to paradoxical activation of the MAPK pathway; the combination has now become the standard of care in patients with …
What drugs are MEK inhibitors?
MEK inhibitors include trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi). These drugs can be used to treat melanoma that has spread or can’t be removed completely.
What does BRAF inhibitor mean?
BRAF is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf.
How do MEK inhibitors work?
MEK inhibitors bind to and inhibit MEK, inhibiting MEK-dependent cell signaling. This inhibition leads to cell death and the inhibition of tumor growth. These are allosteric binding inhibitors of MEK which inhibit either MEK1 alone, or both MEK1 and MEK2.
What is BRAF responsible for?
The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell’s nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions.
What does BRAF positive mean?
A BRAF mutation is a change in a BRAF gene. That change in the gene can lead to an alteration in a protein that regulates cell growth that could allow the melanoma to grow more aggressively. Approximately half of melanomas carry this mutation and are referred to as mutated, or BRAF positive.
Is MEK inhibitor chemotherapy?
A new class of chemotherapeutic agents, MEK inhibitors, has recently been developed and is proving to be an effective treatment for a number of cancers.
What are the side effects of MEK?
MEK Inhibitor Side Effects The most common adverse effects of MEK inhibitors (e.g., trametinib) are rash, diarrhea, peripheral edema, fatigue, and dermatitis acneiform. MEK inhibitors also have unique cardiac and ophthalmologic side effects. Central serous retinopathy can occur during treatment with trametinib.
Is BRAF mutation more aggressive?
Even though BRAF-positive melanomas can be more aggressive, many factors can affect the risk of your melanoma coming back.
Are there any BRAF / MEK inhibitors that are tolerable?
Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management The inhibition of the mitogen-activated protein kinases signalling pathway through combined use of BRAF and MEK inhibitors (BRAFi+MEKi) represents an established therapeutic option in patients with BRAF-mutated, advanced melanoma.
Is there a combination therapy for BRAF and MEK?
In an attempt to delay resistance to BRAF inhibition and explore the safety of combination therapy with BRAF and MEK inhibition, we conducted a phase 1 and 2 study to investigate the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib in patients with metastatic BRAF V600 melanoma.
How are BRAF and MEK inhibited in melanoma?
Part C was a phase 2 study in which patients were randomly assigned in a 1:1:1 ratio to receive 150 mg of dabrafenib twice daily plus once-daily trametinib, at a dose of either 1 mg (combination 150/1) or 2 mg (combination 150/2), or 150 mg of dabrafenib monotherapy twice daily.
How long does MEK inhibitor trametinib take to work?
Treatment with the MEK inhibitor trametinib has also shown similar PFS (4.8 months) and response rates (48%) when administered as first-line therapy in this patient population [Flaherty et al. 2012b].