Cancer genetics

Question 1

3 things that lead to more mutations in cancer cells vs normal cells

Answer 1

proliferation, loss of p53, and genomic instability

Question 2

List some things that result from clonal expansion in cancer cells

Answer 2

increased survival, proliferation, tumor propagating potential, metastasis, chemotherapy resistance

Question 3

Which has more genomic instability and CNVs, localized or metastatic cancers?

Answer 3

metastatic

Question 4

What is the “magic bullet”?

Answer 4

Gleevec (imatinib) that treats blood cancer

Question 5

What do 95% of CML patients have?

Answer 5

philadelphia chromosome

Question 6

Hybrid Bcr-Abl protein results in constitutive activation of what?

Answer 6

Tyrosine Kinase of abl

Question 7

What does Gleevec inhibit?

Answer 7

Tyrosine kinase of abl

Question 8

Why is Gleevec so effective?

Answer 8

Normal cells have non-abl tyrosine kinases, which allows them to continue to function even when the abl TKs are inhibited, while the cancerous cells only have the abl-fusion TKs

Question 9

What is another example of chromosomal translocation gene fusion inhibitor anti-cancer therapy?

Answer 9

Larotrectinib, an NTRK inhibitor, for solid tumors with NTRK gene fusions in prostate cancers

Question 10

These kinds of chemo drugs add an alkyl group to DNA, cause DNA damage, and stop DNA replication

Answer 10

Alkylating agents and platinum based drugs (cisplatin, carboplatin)

Question 11

These chemo drugs disrupt microtubule functions

Answer 11

Taxanes

Question 12

This type of chemo drugs inhibit specific targets within cancer cells

Answer 12

targeted therapy

Question 13

This anti-cancer treatment cannot differentiate btw normal and cancer cells, so it is toxic to all cells, especially rapidly proliferating cells

Answer 13

chemotherapy

Question 14

Proteasome inhibitors and tyrosine kinase inhibitors are examples of what class of drugs?

Answer 14

small molecule inhibitors

Question 15

These drugs bind to intracellular kinase domain and act as competitive inhibitor of ATP binding

Answer 15

Tyrosine kinase inhibitors

Question 16

These drugs target receptors on the surface of cancer cells to prevent receptor activation

Answer 16

Antibody drugs (usually monoclonal abs)

Question 17

these mutations are the primary force for promoting cancer formation and progression, and caused by overexpression, amplification, or mutation

Answer 17

Driver mutations

Question 18

Examples of Driver Mutations

Answer 18

BCR/ABL, ALK fusion gene, EGFR, HER-2, BRAF, Ras, Myc

Question 19

How are cancers often classified for targeted therapies in recent years?

Answer 19

biomarker genetic testing to determine “driver mutations”

Question 20

This gene family is often mutated or amplified in lung and breast cancer

Answer 20

HER/EGFR family

Question 21

The 2 major signaling pathways for EGFR

Answer 21

PI3K/AKT and kRAS/BRAF/MEK/ERK

Question 22

This mutant of HER resembles a ligand-activated state

Answer 22

HER2

Question 23

This class of drugs enters cells and inhibits the intracellular portion of EGFR

Answer 23

TKIs, tyrosine kinase inhibitors (specific for EGFR), including erlotinib and gefitinib

Question 24

This class of drugs does NOT enter a cell and blocks EGFR surface proteins

Answer 24

anti-EGFR mAb drugs, including cetuximab, panitumumab, and nimotuzumab

Question 25

Which targeted EGFR therapy often results in resistance

Answer 25

TKIs

Question 26

What do you need for EGFR with a T790M mutation?

Answer 26

a 4th generation TKI: osimertinib

Question 27

3 things that confer resistance to anti-EGFR therapies

Answer 27

Met receptor activation, PI3K mutation, or Ras mutation

Question 28

Activating kRas mutations are found in which type of cancer?

Answer 28

metastatic colorectal cancer

Question 29

3 methods to detect HER2

Answer 29

immunohistochemistry, PCR, and FISH

Question 30

Mechanism of mAb therapy for Her2

Answer 30

prevents HER2 dimerization, downregulates receptor by endocytic destruction, and induce ADCC by NK cells and macrophages

Question 31

What are some of the ways to stratify BCa patients based on molecular markers?

Answer 31

Hormone receptors (estrogen or progesterone receptors), HER2 status, or triple negative for all 3 (for which you just gotta use chemo and radiation)

Question 32

This gene is involved in dsDNA damage repair and mutations result in breast cancer

Answer 32

BRCA1/2

Question 33

How do PARP inhibitors work to treat BRCA mutant cancers?

Answer 33

It inhibits PARP, which would normally repair single stranded DNA breaks. Without PARP, double stranded breaks occur. Cells with the BRCA1/2 normal will be repaired and survive, while the mutant lines will die.

Question 34

How does the cancer immune checkpoint work?

Answer 34

it’s an intrinsic mchanism that prevents over-activation of T cells

Question 35

How do immune checkpoint anti-cancer therapies work?

Answer 35

target antibodies to PD-1 or PD-L1 which restores the anti-tumor function on T cells. Cancer cells can cause PD-1 to bind with PD-L1 and inactivate the T cell which allows cancer cells to avoid immune attack and proliferate.