Anti-Cancer Agents

Question 1

MOA of methotrexate.

Answer 1

Folic acid analog

• binds to dihydrofolate reductase preventing conversion of dihydrofolate to tetrahydrofolate
• cells are sensitive to this drug in the S phase

Question 2

Name the two taxanes and the MOA of this class.

Answer 2

Paclitaxel
Docetaxel

MOA: bind microtubules and prevent depolymerization into tubulin (which is necessary for the cell to divide into daughter cells)

Question 3

What are the major side effects of the two Taxanes?

Answer 3

Both: myelosuppression
Paclitaxel: neurotoxicity
Docetaxel: fluid retention

Question 4

Name the three vinca alkaloids and the MOA of this class.

Answer 4

1. Vinblastine
2. Vincristine
3. Vindesine

MOA: bind tubulin, preventing spindle formation. This prevents a dividing cell from lining up the chromosomes and the cycle is arrested in metaphase

Question 5

Major side effect of all Vinca Alkaloids (especially vincristine).

Answer 5

Neurotoxicity: fatal if administered intrathecally

Question 6

Name the two derivatives of the Podophyllotoxin and the MOA of this class.

Answer 6

Etoposide (V-16)
Teniposide

MOA: glucoside that blocks the G1 phase and replication in the S phase

Question 7

Indications for Podophyllotoxins.

Answer 7

Formulated as a topical cream for skin cancers and genital warts.

Also given IV or oral for Testicular cancer

Question 8

Name the Anti-tumor antibiotic and the MOA of this drug.

Answer 8

Bleomycin
MOA: not fully understood, it is thought to participate in DNA strand breaks and disruption of DNA synthesis enzymes like Topoisomerase II.

Question 9

Main toxicity associated with Bleomycin.

Answer 9

Tissue necrosis

Question 10

MOA and indication of Leucovorin

Answer 10

MOA: analog of folic acid metabolites

Used to reverse toxicity of anti-folate chemotherapy agents or in conjunction with other chemo agents like Methotrexate and 5-FU

Question 11

MOA of alkylating agents

Answer 11

Covalent bonding of alkyl (hydrocarbon) groups onto mainly nitrogen atoms in the nucleic acid bases. This leads to misreading of the genetic code and/or DNA chain breaks

Ex. Carbonium ion (a molecule with a cationic carbon susceptible to nucleophilic attack by the lone pair on the nitrogen in DNA bases)

Question 12

MOA of cyclophosphamide

Answer 12

MOA: must be activated first by P-450 enzymes in the liver. Cyclophosphamide is converted to aldophosphamide by the P-450 enzymes.

Aldophosphamide diffuses into cell where lysosomes digest it to form:

1. Phosphoramide Mustard-chemo metabolite
2. Acrolein-bladder toxic metabolite

Phosphoramide mustard travels to the nucleus where it cross links both separate DNA strands to each other as well as each DNA strand within the same sequence leading to unstable genetic material and induction of apoptosis

Question 13

Name the 4 Anthracyclines and the MOA of this class.

Answer 13

Doxorubicin
Daunorubicin
Epirubicin
Idarubicin
MOA: Inhibits DNA topoisomerase II preventing DNA dependent RNA synthesis (transcription)

also creates free radicals that are toxic to cell membranes and DNA

Question 14

Major side effects of anthracyclines.

Answer 14

Cardiotoxicity, myelosuppression, amenorrhea, N/V

Doxirubicin turns urine red

Question 15

Name the 3 platinum Analog drugs and the MOA of this class.

Answer 15

Cisplatin
Carboplatin
Oxaliplatin

MOA: diffuses into cells and nuclei, interacts with nitrogen atoms in nucleic acids and causes DNA cross linking making it unstable and sending the cel down an apoptotic pathway

Question 16

Name the side effects of Platinum analogs.

Answer 16

All: neurotoxicity, myelosuppression
Cisplatin: nephrotoxicity

Question 17

How can resistance to Cisplatin occur?

Answer 17

The body responds with increased production of “thiols” called metallothionins and glutathione. These products repair damaged DNA caused by Cisplatin or smoking or UV damage and reverse the effects of these insults.