Oncology PGx

Question 1

What type of mutation does cancer usually have?

Answer 1

Somatic usually, germ and somatic second, Germ-line last

Question 2

5 year survival for Colorectal cancer?

Answer 2

64%

Question 3

5 year survival for mCRC

Answer 3

14%

Question 4

What is KRAS?

Answer 4

Proto-oncogene

Question 5

what happens if KRAS is on?

Answer 5

GTPase state and propagate cell growth and differentiation

Question 6

What is K-ras?

Answer 6

It can be intercellular as well

Question 7

When do you give a EGRF inhibitor?

Answer 7

KRAS -
Cant give is positive

Question 8

What codon is activated in KRAS mutation?

Answer 8

12,13 or 61

Question 9

What happens when you bind EGFR?

Answer 9

Attaches cell surface and turns off the tumor like environment

Question 10

Is EGRF therapy given alone?

Answer 10

No always in combo with a chemotherapy

Question 11

Do we have toxic and dosing data for KRAS positive pt given EGFR?

Answer 11

No

Question 12

KRAS mutation on what codon for mCRC cant receive what?

Answer 12

Codon 12 and 13 and can’t get EGFR therapy

Question 13

What do you give if they have KRAS mutation?

Answer 13

Sotorasib NSCLC

Question 14

What is BCR-ABL?

Answer 14

The fuse of 2 gene (9 and 22) and when fused it shortens one called the Philadelphia chromosome

Question 15

Effect of BCR-ABL?

Answer 15

Speeds up cell division and block DNA repair

Question 16

What are the 3 symptoms phase of CML

Answer 16

Chronic - mild or no
Accelerated - symptoms
Blast - severe symptoms

Question 17

what is first generation TKI and what does it do?

Answer 17

Gleevac (imatinib) - prolongs survival and events
Doesn’t cure and goes back to chronic state

Question 18

How does CML develop imatinib resistant?

Answer 18

BCR-AML point mutation bc of amplification and over expression
Cause point mutation in ATP binding site

Question 19

What is IC50?

Answer 19

Lower the better for mutations

Question 20

What is T315I?

Answer 20

ATP binding site point mutation that is important for drugs

Question 21

What are the 4 mutations we look for in CML and which ones do we worries about?

Answer 21

P-loop, ATP binding site, Catalytic domain, A-loop
P-loop and ATP binding site most common

Question 22

When do we test CML pt?

Answer 22

Accelerated or blast phase

Question 23

When to test when on mediation for CML?

Answer 23

See fails or resistance to imatinib
Same with 2nd gen dasatinib or nilotinib

Question 24

Which drug do i give with mutation T315I?

Answer 24

3 or 4th gen ( ponatibnib or asciminib)
FDA approve for this mutation

Question 25

Where are V299L, T315A, and F317L/V and what drug do i give

Answer 25

ATP binding site mutations and i give Nilotinib over dasatinib

Question 26

Where are Y253H, E255K/V and F359V/Cand what drug do i give

Answer 26

Y and E are P loop and F is a catalytic domain Give Dasatinib over Nilotinib

Question 27

What is HER2 or ERBB2?

Answer 27

Givens a worst prognosis and over expressed

Question 28

How does Trastuzamab work and when do I use

Answer 28

Binds to HER 2 and use only if + for HER 2

Question 29

What are the 2 test that find HER2?

Answer 29

FISH and Hercept test

Question 30

6-MP and TPMT what are the alleles?

Answer 30

3A, 3C and 2

Question 31

What does the Allele changes in TPMT do?

Answer 31

Decrease Allele activities

Question 32

What type of SNP is TPMT?

Answer 32

Non-Synonymous

Question 33

How does TPMT cause toxicity?

Answer 33

Usually make 6 - MeMP but since it is decreased you make 6-TGN which is toxic and drive effectively

Question 34

CPIC guidelines for Homo-TPMT?

Answer 34

Reduce 10 fold 75-10 give 3 times a week

Question 35

CPIC for hetero-TPMT?

Answer 35

Reduce dose 30-80%

Question 36

What is FDA recommendation for TPMT testing?

Answer 36

Recommends testing HOMO- reduce initial dose HETERO - monitor

Question 37

What SNP is NUDT15?

Answer 37

Non-synonymous C>T Loss of function *2 and *3

Question 38

What does NUDT15 do?

Answer 38

Converts 6-TGN to less toxic form Loss of function more cytotoxic effects

Question 39

CPIC for HOMO-NUDT15?

Answer 39

Does to 10mg Daily

Question 40

CPIC for Hetero-NUDT15

Answer 40

30-80% reduction

Question 41

Impact of TPMT and NUD15 on OS?

Answer 41

NONE

Question 42

What is Tamoxifen for?

Answer 42

Prodrug too SERM for ER+ and PR+

Question 43

What is need for Tamoxifen to worK?

Answer 43

2D6 and Endoxifen

Question 44

What does 2D6 *10, 17 and 41 do?

Answer 44

Double digits decreased

Question 45

What does 2D6 *3, 4, 5 and 6 do?

Answer 45

Loss of activity

Question 46

What does 2D6 *1xn and 2xn do?

Answer 46

Can be a ultra metabolized

Question 47

Should we test for tamoxifen?

Answer 47

No recommended bc no OS for null but inconsistencies

Question 48

CPIC for DPYD NM?

Answer 48

No change

Question 49

CPIC for DPYD IM?

Answer 49

Reduce does based on activity score 1- 50% 1.5 - 25-50%

Question 50

CPIC for DPYD PM?

Answer 50

Avoid use

Question 51

Why do we test DPYD and is it worth it?

Answer 51

Yes bc hospiliztion have been related to these toxicities Rn cost neutral soon cost effective Not required rn 5-FU

Question 52

UGT1A1*28 does what?

Answer 52

Reduce enzyme activity for the drug Irotecan

Question 53

What factors do i consider when dosing Irotecan and why?

Answer 53

UGT1A1*28 and strong CYP3A4 inhibitors bc of the dose reduction provides a safer profile for neutropenia