What is a RAF inhibitor?
RAF inhibitor binds preferentially to BRAF and inactivates it, but also causes transactivation of the associated CRAF, enhancing MEK-ERK activation and cellular proliferation. That chemotherapy can both cure and cause cancer is not a new concept.
What is BRAF mutation?
A BRAF mutation is a spontaneous change in the BRAF gene that makes it work incorrectly. A mutation causes the gene to turn on the protein and keep it on, which means certain cells get ongoing signals to keep dividing and no instructions on when to stop. This can lead to development of a tumor.
Does RAS activate BRAF?
Our data provide clear in vitro evidence that certain ATP-competitive inhibitors have an intrinsic ability to activate BRAF kinase independent of other proteins, such as RAS and CRAF, most likely through modifying the kinase domain conformation.
What does a positive BRAF test 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.
What is RAS and Raf?
The Ras/Raf/MAPK pathway is probably the best characterized signal transduction pathway in cell biology. The function of this pathway is to transduce signals from the extracellular milieu to the cell nucleus where specific genes are activated for cell growth, division and differentiation.
What protein activates RAS?
Belonging to the GTPases, ras proteins are activated through the binding of GTP by guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) resulting in transmitting signals in the cells .
What are BRAF and MEK inhibitors?
The MEK gene works together with the BRAF gene, so drugs that block MEK proteins can also help treat melanomas with BRAF gene changes. MEK inhibitors include trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi).