PROPER targeting downstream RTK's Flashcards
what is B-Raf mutation key in
melanoma
what has to happen to a melanocyte to get mutated B-Raf? whats it triggered by
triggered by sun exposure
the melanocyte is initiated which gives the individual may nevi 80% of which will be B-RAF mutant= tumours
what % of nevi will be BRaf mutant
80
how can you increase the amount of B-Raf mutations in nevi
continuous sun exposure
what is the most common B-RAF mutation?
valine-to-glutamic acid mutation at residue 600 (V600E) within the protein
what does the BRAF mutation produce. what does this do
oncogenic protein which has elevated activity and over-activates the MAPK pathway
BRAF(V600E) mutations occurs in approx _% of melanomas and ___% of solid tumours
60
8
what happens to p16 in the braf v600e mutation
it increases in the nevus but then decreases at the rapid growth phase
what is p16. why does it decrease in expression in the rapid growth phase?
a break protein for cell cycle progression
it decreases to allow cell cycle progression and increased proliferation
what is the rapid growth phase- where is the tumour at this point? what happens after this
radio disease maintained in the epidermis of the skin
then goes to vertical growth phase= metastatic
what is a potent mutant BRAF inhibitor?
Vemurafenib
Vemurafenib MOA?
ATP competitive, type 1 small molecule inhibitor of BRAF with antineoplastic activity
selectively binds to ATP binding site of the BRAF(V600E) kinase and inhibits its activity
binding inhibits downstream MAPK signalling
what does vemurafenib treat?
to treat melanoma with BRAFV600E gene mutation when its spread or cannot be removed with surgery
what must the patient have to recieve vemurafenib?
mutant BRAF
What happens on BRAF inhibitor therapy?
initially yields significant reductions in tumour but then resistance occurs
