Cancer Genetics

Question 1

gleevec (imatinib)

Answer 1

inhibits the constitutively active kinase that arises from the philadelphia chromosome (bcr-abl) for treatment of CML

Question 2

oncogene addiction

Answer 2

cancer cells depend on one or a few oncogenes for cell survival, which is a rationale for targeted therapy

Question 3

chemotherapy

Answer 3

acts on DNA to kill proliferating cells (cytotoxic); can not differentiate between normal and cancer cells

Question 4

chemo drugs

Answer 4

alkylating agents and platinum based drugs, topoisomerase inhibitors, taxanes (disrupt MT)

Question 5

targeted therapy

Answer 5

inhibit a specific target in cancer cells - mutant proteins, fusion proteins, etc.

Question 6

targeted therapy drugs

Answer 6

small molecular inhibitors (TKIs and proteasome inhibitors) and antibodies

Question 7

“nib”

Answer 7

tyrosine kinase inhibitors; inhibit ATP from binding for function

Question 8

“mib”

Answer 8

proteasome inhibitors

Question 9

“mab”

Answer 9

monoclonal antibodies; prevent receptor activation

Question 10

driver mutations

Answer 10

primary force for promoting cancer formation and are a potential target for therapy

Question 11

causes of driver mutations

Answer 11

over expression, amplification, mutations

Question 12

examples of driver mutations

Answer 12

BCR/ABL, ALK, EGFR, HER-2, Ras, Myc

Question 13

HER family

Answer 13

epidermal growth factor receptors; frequently mutated in lung and breast cancer due to activation in absence of ligand

Question 14

EGFR’s act via _

Answer 14

tyrosine kinase that phosphorylates factors needed for cell proliferation, survival, invasion, metastasis, and chemo resistance

Question 15

EGFR-mutated cells depend on _

Answer 15

a functional EGFR for their survival, rendering them addicted to the receptor

Question 16

EGFR main pathways

Answer 16

Akt and K-ras–>Mek/Erk

Question 17

HER1 mutation associated with _

Answer 17

non-small cell lung cancer (NSCLC)

Question 18

HER1 mutation hot spots

Answer 18

exon 19-21, corresponding with tyr kinase domain

Question 19

targeting EGFR

Answer 19

EGFR-TK inhibitors and anti-EGFR monoclonal antibodies

Question 20

anti-EGFR mAb’s

Answer 20

prevent ligand from binding and will also cause receptor internalization that leads to degradation

Question 21

mutation resistant to TKIs

Answer 21

T790M in exon 20 of HER1

Question 22

primary resistance

Answer 22

mutation exists in tumor at time of treatment

Question 23

secondary resistance

Answer 23

acquired mutation after treatment

Question 24

common reasons for resistance to TKIs

Answer 24

amplification of Met oncogene allows bypassing of EGFR and PI3K mutations often co-occur with EGFR mutations

Question 25

Osimertinib

Answer 25

can be used in the T790M mutation that is resistant to TKI

Question 26

metastatic colorectal cancer mutation

Answer 26

activating K-ras mutations that are associated with poor response to anti-EGFR

Question 27

HER2 mutation

Answer 27

amplified HER2 expression activates other HER family members in absence of ligands

Question 28

HER2 mutation associated with _

Answer 28

breast cancer

Question 29

Herceptin

Answer 29

monoclonal antibody for treatment of HER2+ breast cancer

Question 30

HER2 detection

Answer 30

immunohistochemistry, PCR, FISH

Question 31

Herceptin mechanism

Answer 31

prevents HER2 dimerization and downregulates HER2 receptor by causing endocytosis and induces ADCC by NK cells

Question 32

HER2+ can also be treated with _

Answer 32

TKIs

Question 33

BRCA1/2

Answer 33

involved in dsDNA damage repair via homologous recombination; tumor suppressors

Question 34

PARP inhibitors

Answer 34

therapy for BRCA mutant cancers

Question 35

PARP inhibitor mechanism

Answer 35

will inhibit the ssDNA repair mechanism, causing a dsDNA break –> normal cells will be able to repair this and survive but BRCA mutants can not and will die

Question 36

synthetic lethality

Answer 36

PARP inhibition for BRCA-deficient cancer

Question 37

PD-1/PD-L1 antibodies

Answer 37

restoration of anti-tumor functions of T cells