TyChucks Cancer Chemo Cards

Question 1

Drug combo that treats HER2 (increased aggressiveness) overexpression profile in breast cancer:

1) Blocks receptor action
2) Blocks receptor dimerization

Answer 1

1) Action blocking - trastuzumab

2) Dimer blocking - Pertuxumab

Question 2

Some patients have an abnormally active tyrosine kinase driving proliferation… What tyrosine kinase inhibitors should be used for specific neoplasms?

Answer 2

Imatinib for chronic myeloid leukemia

Gefitinib for non-small cell lung cancer (Epidermal growth factor TK) – screen for specific EGFR mutation profile to see if you’re in 10% that responds extremely well to Gefitinib TK inhibitor

Question 3

Inhibitors of angiogenesis

Answer 3

1) Bevacizumab - mAb against VEGF

2) Sunitinib - TK inhibitor of VEGF (also sorafenib)

Question 4

Suberoylanilide Hydroxamic Acid

Answer 4

Epigenetics: it’s a histone deacetylase inhibitor (HDACi) keeping DNA transcriptionally active so that down-regulated tumor suppressor genes will be re-activated

Question 5

Azacytidine & Decitabine

Answer 5

EpiG: inhibit methylation; thus reactivating innappropriately silenced tumor suppressor genes

Question 6

Methylguanine Methyltransferase (MGMT)

Answer 6

EpiG: MGMT repairs alkylating damage to DNA; theory…methylate MGMT and treat with Temozolomide (alkylating agent) to induce damage and prevent repair

Question 7

High levels of this metabolite in urine are associated with an increased invasion and metastasis

Answer 7

Sarcosine

Question 8

Drug to prevent chemotherapy-induced side effects of headache, dizziness, diarrhea, and constipation

Answer 8

Serotonin Receptor Antagonist (Dolasetron & Palonosetron)

Question 9

MOA of alkylating agents

Answer 9

covalently bind DNA and alter their structure and function… thus NON cycle-active

Question 10

Name the (5) alkylating agents

Answer 10

Chlorambacil
Cyclophosphamide
Carmustin (BCNU)
Busulfan
Mechlorethamine

Question 11

Important chemo drug for chronic leukemias (hint: its also the least toxic alkylating agent)

Answer 11

Chlorambucil

Question 12

Requires metabolism to be active; alkylating agent

Answer 12

Cyclophosphamide

Question 13

lipid soluble alkylating agent (thus great for CNS tumors)

Answer 13

Carmustin (BCNU)

Question 14

alkylating agents used primarily for myelosuppression

Answer 14

Busulfan

Question 15

Non-alkylating, non-cycle active drug that inhibits DNA synthesis and alters template activity… effective against a variety of solid tumors

Answer 15

Gemcitabine

Question 16

Cancer drug analogous to trimethoprim (ie both used to inhibit dihydrofolate reductase thus stopping folic acid synthesis)… gets metabolized by adding glucuronic acid thus making it more water soluble and trapping it intracellularly

Answer 16

methotrexate

Question 17

Used to “rescue” especially bone marrow during methotrexate-induced toxicity

Answer 17

folinic acid

Question 18

Antimetabolites

Answer 18

methotrexate
purine analogues
pyrimidine analogues
***ALL DNA analogues MUST be metabolized to “nucleoside monophosphate” level to be incorporated into cell cycle

Question 19

Purine Analogues

Answer 19

6-mercaptopurine
thioguanine
hydroxyurea

Question 20

Pyrimidine Analogues

Answer 20

5-FU

cytarabine

Question 21

MOA of 5-FU

Answer 21

inhibits thymidylate synthetase enzyme required to make thymidine monophosphate

Question 22

Natural Products to treat cancer

Answer 22

Paclitaxel (taxol)*
vincristine*
vinblastine *
etoposide
toptecan

• = blocks mitosis!!!

Question 23

Vincristine

Answer 23

remission, acute leukemia

advantage = minimal myelo suppression

Question 24

Vinblastine

Answer 24

solid tumors, Hodgkins disease, testicular tumors

adv = less neuro toxic

disadv = myelosuppressive

Question 25

Natural chemo drugs (2 of em) analogous to fluoroquinolones and their specific cancer uses

Answer 25

MOA: inhibit topoisomerases ===> DNA strand break

1) etoposide for testicular cancer
2) topotecan for ovarian and lung cancer

Question 26

List the 4 natural antibiotics that act as cancer chemo drugs

Answer 26

1) doxorubicin
2) actinomycin D
3) Bleomycin
4) Mitomycin

Question 27

natural antibiotic… inhibits RNA polymerase; non-cycle active… VERY toxic

Answer 27

Actinomycin D

Question 28

natural antibiotic… mix of drugs that breaks DNA strands… NON-cycle active… unique toxicity = pulmonary fibrosis

Answer 28

Bleomycin

Question 29

natural antibiotic that inhibits topoisomerases… thus is cycle-active… and cardiotoxic ===> arrythmias and CHF

Answer 29

Doxorubicin

Question 30

natural antibiotic that is an alkylating agent… works against solid tumors

Answer 30

Mitomycin

Question 31

Tamoxifen

Answer 31

Metabolized via CYP2D6 in the liver to endoxifen…. this MUST occur to be active

IF pt is taking another drug metabolized by cyp2d6 (ie anti-depressants like paxil, prozac…) this metabolism will be slowed down and it won’t be as effective

**MOA = anti-estrogen!!! ***

Question 32

Exemestane & Anastrozole

Answer 32

MOA = aromatase inhibitors

thus aid in ER+ breast cancers… because they inhibit formation of estrogen to slow the proliferation that is typically induced by estrogen in such cancers

Question 33

oral antiandrogen that prolongs life especially in men with metastatic prostate cancer

Answer 33

Flutamide

MOA = blocks uptake of androgens

MUST be given with leutinizing hormone releasing hormone analogue (ie leuprolide)

Question 34

Platinum-containing drug that works similiarly to alkylating agens by causing DNA breaks… severe nephrotoxicity

Answer 34

Cis”plat”in – discovered at MSU

Question 35

Cycle-active drug that inhibits ribonucleotide reductase resulting in an inhibition to go for ribo to deoxyribo…. thus inhibiting BOTH purine and pyrimidine synthesis

Answer 35

Hydroxyurea!

Question 36

why is there typically an outgrowth of resistant subpopulations? (don’t overthink it)

Answer 36

tumors are heterogeneous… and any cells within the tumor that are resistant (which is likely) will survive to re-populate a new tumor that is unaffected by such treatment