Chapter 38: Cancer Genome Synthesis

Question 1

What drug treats skin cancer (topical) by inhibiting thymidylate synthase leading to a thymineless cell death, and interfering with protein synthesis by being incorporated into mRNA?

Answer 1

5-fluorouracil

Question 2

What combo is 1st line for colorectal cancer?

Answer 2

“leuovorin”: 5-FU and folinic acid

Question 3

What is the orally available prodrug of 5-fluorouracil that is used to treat metastatic colorectal cancer and 2nd line for breast cancer?

Answer 3

capecitabine (5-FU becomes “FUC”/fuck)

Question 4

What drug is a folate analogue that inhibits thymidylate synthase by binding to the methylenetetrahydrofolate (cofactor) site of the enzyme, and is administered with folic acid and vitamin B12 to reduce GI toxicity?

Answer 4

pemetrexed

Question 5

What drug is used to treat malignant pleural mesothelioma in combination with cisplatin?

Answer 5

pemetrexed

Question 6

What drug inhibits IMPDH, treats ALL, but has increased toxicity/effectiveness with allopurinol?

Answer 6

6-mercaptopurine

Question 7

Which prodrug of 6-MP inhibits IMPDH and is used for immunosuppression of autoimmune diseases?

Answer 7

azathioprine (6-MP becomes “MAP”)

Question 8

What drug inhibits IMPDH and is a selective inhibitor of adenosine deaminase, used to treat hairy cell leukemia and T-cell lymphoma?

Answer 8

pentostatin

Question 9

What drug is an inhibitor of ribonucleotide reductase (RNA –> DNA) by scavenging a tyrosyl radical at the active site of an enzyme?

Answer 9

hydroxyurea

Question 10

What drug treats and treats polycythemia vera, fibrocytosis, and controls blood counts in AML, and causes secondary leukemia with long-term use?

Answer 10

hydroxyurea

Question 11

What does the drug thioguanine inhibit and what is it used to treat?

Answer 11

DNA polymerase (as all purine and pyrimidine analogues do, this one being a guanine analog), and AML

Question 12

What side effects should be looked out for with thioguanine?

Answer 12

myelosuppression, intestinal perforation, hepatotoxicity

Question 13

What is the composition and mechanism of fludarabine phosphate?

Answer 13

purine (adenosine and guanine) analog, inhibits DNA polymerase AND ribonucleotide reductase

Question 14

What is the composition and main side effect of cladribine?

Answer 14

adenosine analogue (clADribine)
- febrile neutropenia

Question 15

What treats hairy cell leukemia?

Answer 15

pentostatin, cladribine

Question 16

What is the composition and main side effects of cytarabine?

Answer 16

cytidine analogue (CYTarabine)
- neuropathy & nephrotoxicity

Question 17

What is the composition and main side effect of azacytidine?

Answer 17

cytidine analogue (azaCYTidine)
- renal failure

Question 18

Main drug used to treat myelodysplastic syndrome?

Answer 18

azacytidine

Question 19

What is the composition and main side effects of gemcitabine?

Answer 19

cytidine analogue (gemCITabine)
-  febrile neutropenia, pulmonary toxicity, HUS, & hepatotoxicity

Question 20

What are the main side effects of fludarabine phosphate?

Answer 20

aplasia of skin, autimmune hemolytic anemia, neurotoxicity

Question 21

What is the main treatment for pancreatic cancer?

Answer 21

gemcitabine

Question 22

What drug for autoimmune diseases crosslinks DNA via bis-alkylation?

Answer 22

cyclophosphamide

Question 23

There is a cancer drug that causes hemorrhagic cystitis, alopecia, GI disturbance, and amenorrhea. What metabolite of the drug does this and what should it be coadministered with to avoid the 1st symptom?

Answer 23

acrolein (metabolite of cyclophosphamide); administer with mesna

Question 24

What alkylating cross-linking nitrosurea also attaches a carbamoyl group to proteins, and is used for brain cancer?

Answer 24

carmustine

Question 25

What crosslinking alkylating agent treats prostate cancer, but should not be used with thromboembolic disorder?

Answer 25

estramustine

Question 26

What crosslinking alkylating agent is good for hypoxic tumors (i.e. at the center of a solid tumor, usually gastric or pancreatic)?

Answer 26

mitomycin

Question 27

What crosslinking alkylating agent is used for bladder cancer but should not be used with hepatic/renal/bone marrow dysfunction (because powerful!)?

Answer 27

thiotepa

Question 28

What crosslinking alkylating agents are used for Hodgkin's disease?

Answer 28

dacarbazine, procarbazine

Question 29

What crosslinking alkylating agent is used for glioblastoma multiforme with radiation, and is a derivative of dacarbazine?

Answer 29

temozolomide

Question 30

What crosslinking alkylating agent treats ovarian cancer but shouldn't be used with neurologic toxicity?

Answer 30

altretamine

Question 31

What crosslinking alkylating agent treats germ cell testicular cancer and is coadministered with mesna to avoid hemorrhagic cystitis?

Answer 31

ifosfamide

Question 32

What in the body can deactivate crosslinking alkylating agents, leading to resistance?

Answer 32

glutathione

Question 33

What crosslinks GUANINE bases that treats genitourinary cancers? What can it be coadministered with to limit its side effect of nephrotoxicity?

Answer 33

cisplatin, carboplatin. | - amifostine (for cisplatin's nephrotoxicity)

Question 34

What crosslinks GUANINE bases that treats colorectal cancers, and cold temperatures exacerbate neurotoxicity?

Answer 34

oxaliplatin

Question 35

What binds oxygen and chelates iron, and leads to DNA strand breaks through oxidative intermediates? (it treats testicular cancer)

Answer 35

bleomycin

Question 36

Name 4 bleomycin side effects

Answer 36

pulm fibrosis(irreversible, dose limiting), MI, stroke, Raynaud's disease

Question 37

Endings of topoisomerase inhibitors

Answer 37

"-tecan, -bicin, -side, -crine"

Question 38

What drugs inhibit topoisomerase I, leading to DNA strand breakage in the S phase? They have a side effect of life-threatening diarrhea and should NOT be used with Gilbert's syndrome

Answer 38

CAMPTOTHECINS: irinothecan, topothecan ("there CAN only be 1 = topo I")

Question 39

What ARITHROCYCLINES inhibit topoisomerase II, leading to DNA strand breakage in the G2 phase? They cause heart failure and are excreted in bile.

Answer 39

doxorubicin, daunorubicin, epirubicin

Question 40

What EPIPODOPHYLLOTOXINS + one other drug inhibit topoisomerase II, leading to DNA strand breakage in the G2 and S phase? They cause heart problems

Answer 40

EPIPODOPHYLLOTOXINS: etoposide, teniposide other: amsacrine

Question 41

What topoisomerase inhibitor is used for breast cancer?

Answer 41

epirubicin

Question 42

What drugs inhibit microtubule polymerization by being toxic to M phase cells, and bind at (+) ends where there is overlap with GTP binding protein

Answer 42

"vinka alkaloids": vinblastine, vincristine, erbulin

Question 43

What drug is best for METASTATIC testicular cancer, but causes extensive bone marrow suppression?

Answer 43

vinblastine (BLASTS all those metastases)

Question 44

What drug is best for pediatric leukemias, but causes peripheral neuropathy and myelosuppression?

Answer 44

vincristine (kids love CHRIStmas, branches of christmas tree like your limbs = periph neurpathy?)

Question 45

What drug is best for METASTATIC breast cancer, but causes alopecia, myelosuppression, and peripheral neuropathy?

Answer 45

erbulin (BU-BEAUtiful = breasts)

Question 46

What drugs inhibit microtubule depolymerization by arresting cells in mitosis, leading to apoptosis?

Answer 46

"taxanes": paclitaxel(binds to INSIDE of MTs), abraxane, docetaxel (TAXING to keep something polymerized)

Question 47

What drug treats solid tumors of ovarian cancer and should be taken with H1 antagonist & dexamethasone to help with hypersensitivity?

Answer 47

paclitaxel

Question 48

What cancer drug can lead to fluid retention syndrome leading to severe edema, and can be relieved by glucocorticoids?

Answer 48

docetaxel