Why are BRAF and MEK inhibitors used together?
Therefore, the premise behind the subsequent clinical trials combining inhibitors of both MEK and mutant BRAF kinase was that they would help to delay this MAPK-driven acquired resistance and result in longer duration of responses, higher rate of tumor responses, and decrease the toxicities observed from paradoxical …
What does a MEK inhibitor do?
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.
How does BRAF inhibitor work?
The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway that regulates the proliferation and survival of melanoma cells.
What drugs are MEK inhibitors?
To date, four MEK inhibitors have been approved by the United States Food and Drug Administration (FDA), including trametinib, binimetinib, selumetinib, and cobimetinib [19–22].
Is it better to be BRAF positive or negative?
We have demonstrated that BRAF positive patients receiving targeted treatment have significantly better survival than their BRAF negative counterparts.
How long do BRAF and MEK inhibitors work?
However, treatment with a BRAF inhibitor is linked with acquired resistance occurring in half of the patients after approximately six months. Combination of MEK and BRAF inhibitor therapy results in extension of the time to resistance, translating into longer overall survival of treated patients.
What are the side effects of MEK?
* Breathing Methyl Ethyl Ketone can irritate the nose and throat causing coughing and wheezing. * Exposure can cause dizziness, lightheadedness, headache, nausea, blurred vision, and may cause you to pass out. * Repeated high exposure can damage the nervous system and may affect the brain.
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.
Are BRAF inhibitors chemotherapy?
We previously found that BRAF inhibition prevents activation of the DNA-damage repair (DDR) pathway in colorectal cancer thus potentiating the effect of chemotherapy.
What MEK stand for?
methyl ethyl ketone
: a flammable liquid compound C4H8O similar to acetone and used chiefly as a solvent —abbreviation MEK.
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.