What is the mechanism of action of vemurafenib?
Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway.
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.
How does V600E activate BRAF?
The glutamate residue of the mutant therefore functions to activate BRAF by inhibiting the interaction of the BRAF’s glycine rich loop and activation segment, which would ordinarily be inhibitory. The loss of inhibition of BRAF leads to an increase in its basal activity and hence is oncogenic.
How does vemurafenib treat melanoma?
Targeted therapy is cancer treatment that focuses on specific molecules within cancer cells. The drugs work by blocking the function of abnormal molecules to slow the growth and spread of cancer, such as melanoma.
What is vemurafenib used for?
Vemurafenib is used to treat certain types of melanoma (a type of skin cancer) that cannot be treated with surgery or that has spread to other parts of the body. It is also used to treat a certain type of Erdheim-Chester disease (ECD; a disease that causes an overproduction of a type of white blood cells).
What does the BRAF gene do?
The BRAF gene provides instructions to a protein responsible for managing important cell functions related to growth. If there is a mutation in the gene, it stops working correctly and signals cells to divide uncontrollably, which leads to a tumor.
Is vemurafenib chemotherapy?
Zelboraf® is the trade name for the generic chemotherapy drug vemurafenib. In some cases, health care professionals may use the generic name vemurafenib when referring to the trade name Zelboraf®. Drug type: Zelboraf® is a targeted therapy.
What does the V600E mutation do?
A specific mutation (change) in the BRAF gene, which makes a protein that is involved in sending signals in cells and in cell growth. This BRAF gene mutation may be found in some types of cancer, including melanoma and colorectal cancer. It may increase the growth and spread of cancer cells.
What causes BRAF V600E mutation?
A BRAF mutation can be inherited from your parents or acquired later in life. Mutations that happen later in life are usually caused by the environment or from a mistake that happens in your body during cell division. Inherited BRAF mutations are very rare, but they can cause serious health problems.
How effective is vemurafenib?
Vemurafenib has prolonged efficacy in patients with BRAF V600–mutant NSCLC (n = 62), as demonstrated by a 37% overall response rate. Response rates were similar in previously treated and untreated patients.
What type of drug is vemurafenib?
Vemurafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.
What are the mechanisms of resistance to vemurafenib?
Three mechanisms of resistance to vemurafenib (covering 40% of cases) have been discovered: Cancer cells begin to overexpress cell surface protein PDGFRB, creating an alternative survival pathway.
What is the initial formulation of vemurafenib?
Reformulation studies. The initial formulation of vemurafenib consisted of a crystalline powder (that was stabilized with several common pharmaceutical excipients to aid bioavailability) that was filled into capsules that could be delivered orally 92.
How does vemurafenib work for melanoma?
Mechanism of action. Vemurafenib only works in melanoma patients whose cancer has a V600E BRAF mutation (that is, at amino acid position number 600 on the B-Raf protein, the normal valine is replaced by glutamic acid ). About 60% of melanomas have this mutation. It also has efficacy against the rarer BRAF V600K mutation.
What are the possible side effects of vemurafenib?
Vemurafenib treatment is associated with a distinct dermatological toxicity profile, which includes a keratosis pilarislike rash, palmar-plantar dysesthesia, papillomas, and/or cutaneous squamous cell carcinomas. There appears to be a pattern of keratoacanthoma and squamous cell carcinoma development particular to vemurafenib treatment.