Cancer 2

Question 1

How was the Hh/Shh signalling pathway identified?

Answer 1

Through animal models-

drosophila, chick, zebrafish and mouse

Question 2

What does a loss of Shh cause?

Answer 2

Cyclopia

Holoprosencephaly

Question 3

What does cyclopamine do?

Answer 3

Inhibits Smo- which represses the Shh signalling pathway

Caused cyclopia in sheep

Question 4

What usually happens to Shh signalling at the end of development?

Answer 4

It is negatively regulated

E.g- limb bud formation- once the digits are formed- Shh signalling repressed

Question 5

What is the effect of the genes activated by Shh signalling?

Answer 5

Promotes proliferation and stem/progenitor cell renewal

Question 6

What is found in stem cell niches? And why is this important

Answer 6

Carefully controlled level of Shh- achieves a balance of stem cells, proliferating progenitors and differentiating cells

Question 7

What occurs to cause basal cell carcinoma?

Answer 7

Smo mutation leads to constant activation of the Shh pathway
Abnormal growth occurs
Cells express Gli1 and Gli2

Question 8

The drug erivedge is based on what compound?

Answer 8

Cyclopamine

Question 9

What does cyclopamine do in terms of Gli1 and 2?

Answer 9

Inactivates the transcription factors Gli1 and Gli2

Question 10

Why is erivedge no longer funded by the NHS?

Answer 10

It is not cost efficient