Melanoma MAPK Flashcards
How many people in the US get melanoma each year?
> 70,000
How many people die from melanoma each year?
8,800
How much more likely are white people to development melanoma than blacks?
10 times
Since 1992, when was the first drug to be FDA approved for melanoma?
2011
How many cancers is Braf mutated in?
50%
What found that Braf was commonly mutated in melanoma?
Human genome project
What Ras mutation is commonly mutated in skin cancer?
N-Ras
How are Ras mutations constitutively active?
Locked into a GTP-active form
Where are the mutations in Raf?
In the kinase domain
What are common mutational effects in the EGFR pathway?
Receptor dimerisation
Intracellular phosphorylation of the receptor
Transphosphorylation of components of the signalling pathway
Why do you not find patients with Braf and Nras mutations?
Since they are in the same pathway they are epistatic
What are Nras mutations?
Undruggable
Under physiological conditions, what does Raf function as?
A dimer
How is the MAPK signalling pathway regulated?
Negative feedback loops:
- ERK inhibits Raf
- ERK inhibits SOS
- ERK inhibits the EGFR
- ERK induces SPRY which inhibits GRB2
In cancer, why do Rafs not need to do to function?
Dimerise