Fun 3

Question 0

Cytarabine

Answer 0

Antimetabolite (S-phase specific)
Converted to triphosphate and incorporated into DNA
Treat AML
Resistance: Increased cytidine deaminase, decreased deoxynucleotide kinase and altered DNA polymerase

Question 1

5-Fluorouracil

Answer 1

Antimetabolite (S-phase specific)
Metabolized to 5-FdUMP - Inhibits thymidylate synthase
Used for solid tumors (pancreas, GI and liver)
Toxicity: Neurotoxicity
Resistance via altered thymidylate synthase

Question 2

Methotrexate

Answer 2

Antimetabolite
Inhibits DHFR (starves cell of both purines and pyrimidines)
Causes accumulation of DHF-polyglutmate, directly blocking purine synthesis
Treat carcinomas, leukemias and lymphomas
Toxicity: Pneumonitis and cirrhosis
Toxicity reduced with leucovorin rescue
Resistance: DHFR amplification, altered DHFR, decreased drug import or increased salvage

Question 3

Leucovorin

Answer 3

Fully reduced folate

Rescues normal cells from methotrexate toxicity

Question 4

Mechlorethamine

Answer 4

Alkylating agent (phase non-specific)
Bifunctional agent
M in MOPP for Hodgkin’s lymphoma treatment
Can cause secondary leukemia

Question 5

Cyclophosphamide

Answer 5

Alkylating agent
Less reactive than mechlorethamine
Requires p450 metabolism in liver (reduces toxicity; allows oral admin.)
Used for leukemia and lymphoma
Toxicity: Hemorrhagic cystitis if patient not hydrated
Can cause secondary leukemia

Question 6

Cisplatin

Answer 6

Platinum complex - “nonclassical” alkylator
Bifunctional agent
Treat testicular cancer and other solid tumors
Nephrotoxicity if patient dehydrated

Question 7

Doxorubicin

Answer 7

Anthracycline
Intercalates into DNA - Redox causes DNA damage
Inhibits topo II
Treat solid tumors
Can cause cardiomyopathy

Question 8

Bleomycin

Answer 8

DNA binder(G2-specific)
Chelates copper and iron - Redox damages DNA
Treat germ cell tumors
Can cause pulmonary fibrosis

Question 9

Irinotecan

Answer 9

Topo I inhibitor (S-phase specific)
Treat solid tumors
Activated to SN-38 - Can cause leukopenia
SN-38 glucuronidated by UGT1A1
Genetic defect in UGT1A1 causes nausea and leukopenia

Question 10

Etoposide

Answer 10

Topo II inhibitor (S-phase specific)
Treat leukemia and lymphoma
Can cause secondary leukemia

Question 11

Vincristine

Answer 11

Prevents microtubule polymerization (M-phase specific)
Directly binds tubulin heterodimers
Can cause peripheral neuropathy
Treat leukemia and lymphoma

Question 12

Vinblastine

Answer 12

Prevents microtubule polymerization (M-phase specific)
Directly binds tubulin heterodimers
Neurotoxic
Treat solid tumors

Question 13

Paclitaxel

Answer 13

Inhibits microtubule depolymerization
Bind to beta tubulin
Treat breast and ovarian cancer (also lung and head/neck)
Can cause “stocking glove” neuropathy

Question 14

Prednisone

Answer 14

Glucocorticoid

Treat leukemias by activating apoptosis

Question 15

Tamoxifen

Answer 15

Selective estrogen receptor modulator
Treat breast cancer (can be prophylactic)
Better for post-menopausal women (less endogenous estrogen)

Question 16

Anastrozole

Answer 16

Aromatase inhibitor
Treat estrogen-sensitive breast tumors
Prevents post-menopausal women producing estrogen from extra-ovarian tissue
More specific than early agents (doesn’t block corticosteroid pathway)

Question 17

Flutamide

Answer 17

Testosterone receptor antagonist
Treat prostate cancer
Used in combination with GnRH agonist

Question 18

Leuprolide

Answer 18

GnRH agonist
Treat prostate cancer
Cause transient release of FSH and LH (blocked by flutamide)
Long-term feedback inhibition of testosterone release
Daily subQ admin.

Question 19

Imatinib

Answer 19

Bcr-Abl inhibitor
Treat CML (t9:22)
Diffuses into cell to inhibit tyrosine kinase

Question 20

Bevacizumab

Answer 20

VEGF inhibitor
Humanized monoclonal antibody
Treat colorectal cancer
Can increase bleeding and cause slow wound healing

Question 21

Interluekin-2

Answer 21

Stimulates generation of killer T-cells

Approved for melanoma; active for other tumors and leukemia

Question 22

Bortezemib

Answer 22

Proteasome inhibitor
Stabilizes IkB - Inhibits NFkB preventing growth
Treats multiple myeloma

Question 23

Tretinoin

Answer 23

All-trans retinoic acid (ATRA)
Cofactor of RAR-RXR dimer - Displaces repressor of differentiation
APL has RAR-PML mutation decreasing APL affinity for dimer
Pharmacologic doses overcomes APL mutation
Can cause pulmonary distress via inflammation

Question 24

Thalidomide

Answer 24

Inhibits angiogenesis and stimulates immune system (blocks VEGF, TNF and IL-6 production)
Treat multiple myeloma
Can cause birth defects

Question 25

Colony-stimulating factors

Answer 25

EPO, G-CSF and GM-CSF

Promote growth of bone marrow cells to prevent toxic effects of cytotoxic agents - Attenuate myelosuppression and anemia