erivedge

Question 1

what is the drug name for erivedge?

Answer 1

vismodejib

Question 2

when were one eyed lambs discovered?

Answer 2

1940s/50s

- from eating corn lillies

Question 3

when was the compound in corn lillies identified?

Answer 3

1960s/70s

- cyclopamine

Question 4

was does cyclopamine do?

Answer 4

directly bind and inhibit smo

inhibit Shh signalling as smo needs to be activated for shh signalling to occur

Question 5

what genes are activated by the Shh pathway?

Answer 5

genes which regulate cell cycle - cause proliferation and stem/progenitor cell renewal
e.g. myc, cyclined1, bcl-2(anti-apoptotic), sox2, nanog

Question 6

what niche is shh expressed in?

Answer 6

skin stem cell niche

- levels of shh are regulated by bmps and wnts - stem cells repsond to this - in bottom of crypt like structures

Question 7

what can GOF in smo lead to?

Answer 7

BCC (basal cell carcinoma)
(most common form of skin cancer)
-shh pathway relevent to 90% cases

Question 8

what loss of function mutations lead to bcc?

Answer 8

LOG mutations in ptc (2lof required) can lead to BCC

-ptc repressed smo- when PTc is non-functional Smo is always derepressed - increased shh expression

Question 9

what is vismodejib?

Answer 9

a cyclopamine competative antagonist of smo
(shh pathway inhibitor)
- improved BCC but too expensive