Cancer Drugs: Antimetabolites and Antibiotics

Question 1

Antimetabolite drugs (MTX, 5-FU, 6-MP, etc.) work during what phase of the cell cycle?

Answer 1

S phase, when DNA is being synthesized

Question 2

Methotrexate (MTX) is a ______ analog which works by inhibiting ______ which directly reduces levels of ________

Answer 2

Folic Acid
Dihydrofolate reductase
dTMP (thus reducing DNA synthesis)

Question 3

What type of tissue in the body is most susceptible to anticancer therapy?

Answer 3

Labile tissue
this type never sits in the G0 phase
Ex: bone marrow, GI epithelia, skin, hair follicles

Question 4

Describe the primary side effect of methotrexate and any drugs that can reverse it.

Answer 4

Myelosuppression

Can be reversed with Leucovorin

Question 5

5-Fluorouracil (5-FU) is a _______ analog which works by inhibiting ________ which directly reduces levels of ________

Answer 5

pyrimidine
thymidylate synthase
dTMP (thus reducing DNA synthesis)

Question 6

Describe the primary side effect of 5-FU and any drugs that can reverse it.

Answer 6

Myelosuppression

reversible with thymidine

Question 7

6-Mercaptopurine (6-MP) must be metabolized by what enzyme?

Answer 7

Xanthine oxidase
Recall: this enzyme is blocked by allopurinol, tx for gout
therefore, allopurinol increases 6-MP toxicity (myelosuppression, GI, liver)

Question 8

Name a precursor of 6-MP and its use in medicine.

Answer 8

Azathioprine is a 6-MP precursor.

It has the same effects, but is used in kidney transplants

Question 9

6-MP is activated by ________ and is a _______ analog.

Answer 9

HGPRTase

purine analog

Question 10

What drug has the same mechanism as 6-MP but can be given with allopurinol?

Answer 10

6-thioguanine (6-TG)

Question 11

What drug is a pyrimidine analog that inhibits DNA polymerase?

Answer 11

Cytarabine (ara-C)

Question 12

What are the antitumor antibiotics?

Answer 12

Dactinomycin, doxorubicin, daunorubicin, bleomycin, etoposide, teniposide

Question 13

Dactinomycin is used for what types of tumor?

Answer 13

Childhood tumors (kids ACT up)
Ex: Wilm's tumor of kidneys, Ewing's sarcoma of bones, rhabdomyosarcomas

Question 14

How does dactinomycin work?

Answer 14

Wedges itself between DNA base pairs (“intercalates”).

Question 15

Doxorubicin/daunorubicin does what 2 things to combat tumors?

Answer 15

creates free radicals

noncovalently wedges btw base pairs

Question 16

What is the major worry when taking doxorubicin/daunorubicin? How do we combat this?

Answer 16

Cardiotoxicity
why? heart cells are susceptible to free radicals!
Dexrazoxane used to prevent it

Question 17

What is bleomycin’s MOA as an anti-tumor?

Answer 17

induces free radical formation

Question 18

What toxicities come with bleomycin?

What cancer type is it most often used for?

Answer 18

pulmonary fibrosis

used for testicular cancers

Question 19

Etoposide/teniposide inhibit _______ which does what?

Answer 19

inhibits topoisomerase II (DNA gyrase)

increases degredation of the DNA

Question 20

What class of antibiotics has the same mechanism as Etoposide?

Answer 20

Fluoroquinolones (they also inhibit topoisomerase IV fyi)