Antineoplastics Mechanism of Action

Question 1

methotrexate

Answer 1

folate analog, inhibits dihydrofolate reductase and dec. dTMP

Question 2

5-fluorouracil

Answer 2

pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. Inhibits thymidylate synthase leading to dec. dTMP

Question 3

cytarabine *arabinofuranosyl cytidine)

Answer 3

pyrimidine analog leading ton inhibition of DNA polymerase

Question 4

azathioprine, 6-mercaptopurine, 6-thioguanine

Answer 4

Purine (thiol) analogs that decrease de novo purine synthesis. Activated by HGPRT (are they base analogs that turn into nucleotide purine analogs?-yes they are)

Question 5

Azathioprine and 6-MP relation

Answer 5

Azathioprine is the pro-drug

Question 6

Dactinomycin (actinomycin D)

Answer 6

Intercalates in DNA

Question 7

Doxorubicin (adriamycin), daunorubicin

Answer 7

generates free radicals. Intercalates DNA, breaks in DNA

Question 8

Bleomycin

Answer 8

induces free radical formation, which causes breaks in DNA strands

Question 9

Cyclophosphamide, ifosfamide

Answer 9

covalently X-link (interstrand) DNA at guanine N-7. Require bioactivation by liver.

Question 10

Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

Answer 10

Require bioactivation. Crosses Blood brain barrier, cross links DNA.

Question 11

busulfan

Answer 11

cross-links DNA

Question 12

vincristine, vinblastine

Answer 12

Vinca alkaloids that bind beta-tublin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest)

Question 13

Paclitaxel, other taxols

Answer 13

Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur) [taxing to stay polymerized]

Question 14

cisplatin, carboplatin

Answer 14

cross-link DNA

Question 15

etoposide, teniposide

Answer 15

eTOPOside inhibits TOPOisomerase II increases DNA degradation

Question 16

irinotecan, topotecan

Answer 16

inhibit topoisomerase I and prevent DNA unwinding and replication

Question 17

hydroxyurea

Answer 17

inhibits ribonucleotide reductase, dec. DNA synthesis (S-phase specific)

Question 18

prednisone, prednisolone

Answer 18

triggers apoptosis, even in nondividing cells

Question 19

tamoxifen, raloxifene

Answer 19

SERMs: receptor antagonists in breast and agonists in bone. Block binding of estrogen to ER+ cells.

Question 20

trastuzumab (herceptin)

Answer 20

Monoclonal Ab against HER-2 (c-erbB2), tyrosine kinase receptor. helps kill breast CA cells that overexpress HER-2, through inhibition of HER2-initiated cellular signaling and Ab dependent cytotoxicity

Question 21

Imatinib (Gleevec)

Answer 21

tyrosine kinase inhibitor of bcr-abl (philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)

Question 22

Rituximab

Answer 22

Monoclonal Ab against CD20, found on most B-cell neoplasms

Question 23

Vemurafenib

Answer 23

small molecule inhibitor of forms of the B-Raf kinase with the V600E mutation.

Question 24

Bevacizumab

Answer 24

Monoclonal antibody against VEGF. Inhibits angiogenesis.

Question 25

The Antimetabolites

Answer 25

MTX, 5-FU, Cytarabine, Azathioprine, 6-MP, 6-TG

Question 26

The Antitumor antibiotics

Answer 26

Dactinomycin, Doxorubicin, Bleomycin

Question 27

The Alkylating agents

Answer 27

Cyclophosphamide, nitrosoureas, busulfan

Question 28

The Microtubule inhibitors

Answer 28

Vinca alkaloids and taxols