Response to chemotherapy

Question 1

What is 5-FU metabolised by

Answer 1

DPYD

Question 2

What are the 5-FU side effects

Answer 2

myelosuppression (bone marrow), cardiac issues, diarrhoea

Question 3

How much 5-FU is metabolised before it can exhibit its action in wild type patients

Answer 3

80% therefore patients have to be essentially overdosed with the drug so the remaining 20% can have an effect

Question 4

What common polymorphisms are associated with DPYD

Answer 4

Reduced activity:
A->T Asp->Val
G->A Haplotype B3

Null activity
DPYD*2A splicing defect
T->G *13

Question 5

What is Irinotecan and Cytarabine metabolised by

Answer 5

UGT1A1

Question 6

Variants in UGT1A1 are associated with

Answer 6

Gilbert’s syndrome

Question 7

Molecular basis of UGT1A1 polymorphism

Answer 7

UGT1A1*28
has 7 TA repeats
(normally 6 TA repeats)

Question 8

What are thoipurines metabolised by

Answer 8

TPMT

Question 9

What allele of TPMT is wild type and what are the most common defective alleles

Answer 9

*1 is wildtype
*2 and *3 are defective

Question 10

What is Imatinib

Answer 10

A tyrosine kinase for ABL-activated cancer like CML

Question 11

What causes Imatinib resistance

Answer 11

Mutations of the Bcr-ABL kinase domain
Especially T315 mutation (right in the APT binding domain)

Question 12

What affects Gemtuzumab metabolism

Answer 12

CD33 polymorphism

Question 13

Molecular basis of the CD33 polymorphism

Answer 13

C->T
exon skipping
exon 2 missing
drug doesn’t recognise isoform

Question 14

What polymorphism affects Trastuzamab action

Answer 14

In HER2 (tyrosine kinase)