Quiz 6 (oncology)

Question 1

Geftinib drug target

Answer 1

EGFR

Question 2

Erlotinib drug target

Answer 2

EGFR

Question 3

Afarinib drug target

Answer 3

EGFR

Question 4

Crizotinib drug target

Answer 4

Receptor tyrosine kinase/ALK

Question 5

Ceritinib drug target

Answer 5

Receptor tyrosine kinases/ALK

Question 6

Cetuximab drug target

Answer 6

EGFR/KRAS

Question 7

Panitumumab drug target

Answer 7

EGFR/KRAS

Question 8

Which oncology meds are used for colorectal cancer?

Answer 8

Cetuximab

Panitumumab

Question 9

Which oncology med is used for head and neck cancer?

Answer 9

Cetuximab

Question 10

What are the majority of oncology meds used for?

Answer 10

Lung cancer

Question 11

EGFR activation leads to cell ____

Answer 11

proliferation

Question 12

What are the 2 types of lung cancer classifications?

Answer 12

Non-Small Cell Lung Cancer

Small Cell Lung Cancer

Question 13

Which type of lung cancer is more common?

Answer 13

Non-Small Cell Lung Cancer (NSCLC)

Question 14

What is traditional first-line therapy for NSCLC?

Answer 14

Platinum-based chemotherapy

Question 15

Activation/inactivation of EGFR causes cancer?

Answer 15

activation

Question 16

HER1/ErbB1 mutations in EGFR predict _____ may be more effective.

Answer 16

TKI Inhibitors

Question 17

If mutation not present in EGFR, then ____ is more effective.

Answer 17

Chemotherapy

Question 18

What is the structure of EGFR?

Answer 18

Crosses cell membrane
Abs bind outside
Tyrosine kinase inhibitor intracellular

Question 19

What do TKIs do?

Answer 19

Inhibit phosphorylation by tyrosine kinase

Question 20

What factors of a tumor indicate poor prognosis (there are 5)?
EGFR Inhibits all of these

Answer 20

Proliferation
Survival
Angiogenesis (creating its own blood supply)
Migration 
Adhesion

Question 21

Which EGFR mutations indicate susceptibility to TKI?

Answer 21

in exons 18, 19, 21

Question 22

Which EGFR mutations indicate resistance to TKIs?

Answer 22

in exon 20

Question 23

What mutation in exon 19 causes susceptibilty to TKIs?

Answer 23

Deletions

Question 24

What mutation in exon 21 causes susceptibility to TKIs?

Answer 24

L858R mutation

Question 25

What are the EGFR tyrosine kinase inhibitors?

Answer 25

Gefitinib Erlotinib Afatinib

Question 26

Erlotinib and afatinib are most effective with ___ EGFR expression

Answer 26

higher

Question 27

T/F: Gefitinib had a survival benefit in patients who had high levels of EGFR

Answer 27

False - fast-track approval has failed

Question 28

When are erlotinib and afatinib first-line treatment?

Answer 28

``` exon 19 deletions exon 21 (L858R) substitution mutations ```

Question 29

What is the barrier to using genotype guided dosing with TKIs?

Answer 29

It's desired to begin therapy before genotype results are available

Question 30

Which meds are antibodies against overexpressed EGFR?

Answer 30

Cetuximab | Panitumumab

Question 31

___ mutations are associated with resistance to TKIs in patients with EGFR mutations

Answer 31

KRAS mutations

Question 32

T/F: Activation of KRAS proteins would cause cancer development regardless of EGFR signaling

Answer 32

True - EGFR signaling is upstream of KRAS

Question 33

Cetuximumab/Panitumumab are used in patients with ______ colon cancer and _______

Answer 33

EGFR-expressing colon cancer; KRAS mutant negative

Question 34

ALK mutation is fusion of the ____ gene to ____

Answer 34

ALK to EML4 (which is constitutively promoted, so makes ALK always active)

Question 35

What are the ALK inhibitors?

Answer 35

Crizotinib | Ceritinib

Question 36

Which ALK inhibitor is first-line for ALK positive NSCLC patients?

Answer 36

Crizotinib

Question 37

Crizotinib increases he risk of ___ adverse effect over chemotherapy

Answer 37

hepatotoxicity (increased LFTs)

Question 38

When is ceritinib used?

Answer 38

If crizotinib fails

Question 39

What ADE with ceritinib?

Answer 39

Increased LFTs

Question 40

What is the mechanism of mercaptopurine?

Answer 40

inhibits purine nucleotide synthesis

Question 41

What gene is associated with mercaptopurine?

Answer 41

TPMT

Question 42

What gene is associated with irinotecan?

Answer 42

UGT1A1

Question 43

What is the MOA of irinotecan?

Answer 43

Inhibits topoisomerase I

Question 44

___ TPMT activity increases the risk of _____ toxicity

Answer 44

Low; mercaptopurine toxicity

Question 45

What is mercaptopurine toxicity?

Answer 45

Myelosuppression (reduced WBC, RBC, platelets)

Question 46

When is irinotecan used?

Answer 46

Metastatic colorectal cancer

Question 47

What is the active metabolite of irinotecan?

Answer 47

SN-38

Question 48

___ inactivates SN-38

Answer 48

UGT1A1/6/9

Question 49

Which UGT1A1 allele decreases function?

Answer 49

*28

Question 50

What does decreased UGT1A1 function increase the risk of with irinotecan?

Answer 50

Neutropenia and severe (deadly) diarrhea

Question 51

How should you adjust irinotecan dosing for patients with UGT1A1*28?

Answer 51

Reduce by 1 dose level

Question 52

Is genotyping for UGT1A1 normally done?

Answer 52

No - no clear dosing guidelines

Question 53

Most familiar cancer syndromes are related to tumor suppressor genes or oncogenes?

Answer 53

Tumor suppressor genes

Question 54

What is loss of heterozygosity?

Answer 54

Losing chromosomes - maybe 23, maybe just part of some of them - but only have 1 copy left of a gene

Question 55

Heritable retinoblastama is autosomal dominant or recessive?

Answer 55

Dominant

Question 56

Herital retinoblastoma is normaly bilateral or unilateral?

Answer 56

Bilateral

Question 57

Average age at diagnosis is younger for pts with nonheritable or heritable retinoblastoma?

Answer 57

Heritable

Question 58

T/F: Retinoblastoma follows the two-hit hypothesis model

Answer 58

TRUE

Question 59

The RB1 gene (involved in retinoblastoma) is involved in ______ when normally functioning

Answer 59

Cell cycle regulation

Question 60

P53 prevents cell from completing cell cycle if what?

Answer 60

DNA or cell is damaged

Question 61

How does p53 stop cell cycle if damage is minor?

Answer 61

Halts until it can be repaired

Question 62

How does p53 stop cell cycle if damage is major?

Answer 62

If it cannot be repaired, commits apoptosis