genetic changes in cancer and modern treatment

Question 1

What is an oncogene?

Answer 1

• gain of function in a gene usually involved in positive regulation of growth
• dominant mutation

Question 2

What is a tumour suppressor gene?

Answer 2

• characterised by a loss of function mutation in a gene usually involved in negative regulation of growth
• recessive mutation

Question 3

What is a proto-oncogene?

Answer 3

• wild-type/unmutated form of a gene that positively regulates growth

Question 4

What are mutator genes?

Answer 4

genes normally responsible for DNA repair

Question 5

What is chronic myeloid leukaemia (CML) caused by?

Answer 5

• a translocation event between chromosome 9 and 22 (philadelphia chromosome)
• results in production of unique tyrosine kinase termed BCR-ABL

Question 6

Which drug is used to treat chronic myeloid leukaemia and how does it do this?

Answer 6

• imatinib is a selective inhibitor of the unique tyosine kinase

Question 7

What is the problem with imatinib?

Answer 7

• resistance
• most common mechanism of resistance is emergence of ABL kinase domain mutations

Question 8

What is the other name for herceptin?

Answer 8

trastuzumab

Question 9

How can HER2+ breast cancer patients be treated?

Answer 9

• herceptin, linked to microtubule inhibitor DM-1
• blocking dimerisation of HER2 with pertuzumab

Question 10

How can Venetoclax be used against cancer?

Answer 10

• a lot of tumours over express the anti-apoptotic protein BCL2
• venetoclax is a BH3 mimetic drug