Wk 4 - Personalized Medicine

Question 1

What are 3 benefits of personalized medicine?

Answer 1

1. More cost effective
2. Targets patient in a more personal way to prevent some negative side effects
3. Dosages based on patient’s genetics

Question 2

Pharmacogenetics

Answer 2

Study of how an individual’s genetic inheritance affects the body’s response to drugs

• This helps with diagnosis, treatment, prediction of outcome, drug response

Question 3

Pharmacogenomics

Answer 3

Intersection of pharmaceuticals and genetics

• Decoding drug responsiveness

Question 4

Which alleles should be looked at before prescribing warfarin?

Answer 4

• VKORC1 = vitamin K epoxide reductase
• CYP2C9 = cytochrome p450 C29

Have big impact on warfarin sensitivity

Question 5

What is a SNP?

Answer 5

Naturally occurring variation in DNA sequence that may/may not ∆ the protein’s function

Question 6

How do you detect a SNP?

Answer 6

• Deep sequencing - sequence genome SEVERAL times to get most accurate read
• Exon trapping - sequence just the 2% of eons and looking super close there
• Direct sequencing - sequence genome normally (not many times) – this is most common

Question 7

T/F CP450 enzymes help with metabolism of half of all medications

Answer 7

True

Question 8

P450 codeine metabolism

Answer 8

• NEED 3A4 and 2D6 in order to metabolize codeine
• Most people have a good balance of the 2 and can do it fine

Some drugs inhibit codeine metabolism
Ex: Quinidine (reduces 2D6) – treats malaria and arrhythmias

Question 9

Poor metabolizers

Answer 9

• Can’t metabolize codeine because of a mutated 2D6

- ∆ shape of 2D6 so drug can’t fit into enzyme pocket for metabolism

Question 10

Extensive metabolizers

Answer 10

• Good balance between 3A4 and 2D6 and can metabolize codeine to morphine just fine

Question 11

Ultrarapid metabolizers

Answer 11

• ∆ shape of 2D6 so that metabolism of codeine happens too fast
• No pain relief

Question 12

Codeine metabolism review

Answer 12

2D6 > 3A4 = can convert codeine to morphine (but don’t want 2D6 to be too high or you’ll be ultra rapid)

2D6 < 3A4 = can’t convert codeine to morphine and instead converts to nor codeine :(

Question 13

What does grapefruit juice do?

Answer 13

Reduces 3A4 – can make person not able to metabolize codeine

Question 14

When would we need to do a genetic test before cancer therapy?

Answer 14

• When treatment is specialized and expensive

- Ex: EGFR example where only 10% have a responsive cell surface receptor

Question 15

How to do genetic test for cancer therapies

Answer 15

• Sequencing
• Microdissection: remove part of tumor and cut into very thin slices (H and E) and pathologist isolates DNA to sequence using PCR or direct amplification