Antineoplastics (Koland)

Question 1

why don’t you use antivirals to treat viruses that cause cancer?

Answer 1

because by the time the neoplasm is detected, the virus has already transformed the cells, making them tumor-like

Question 2

True or false: conventional chemotherapeutic agents have high therapeutic indices.

Answer 2

False. These agents have low therapeutic indices, making it impossible to treat tumor cells without harming host cells.

Question 3

Activation of ____ overrides the G1 arrest, pushing a cell back through the cell cycle.

Answer 3

oncogenes

Question 4

Inactivation of these genes overrides the mitotic checkpoint, allowing a cell to proceed through the cell cycle with unchecked damage.

Answer 4

tumor suppressor genes

Question 5

Represents the number of dividing tumor cells to the number of differentiated tumor cells

Answer 5

tumor cell growth fraction

Question 6

why is it important to know a tumor cell growth fraction?

Answer 6

this number will tell you how many dividing tumor cells are present in the tumor and will be responsive to treatment (only cells that are dividing are sensitive to conventional chemotherapeutic agents)

Question 7

these tumor cells that have left the primary tumor are the origin of metastatic growth, and may possibly divide more rapidly, making them sensitive to chemotherapy

Answer 7

micrometastases

Question 8

the ___ is the point of lowest blood cell count in a patient receiving chemotherapy, and represents the window in which the patient is at highest risk for an opportunistic infection.

Answer 8

nadir

Question 9

What is often given with a chemotherapeutic agent to speed the recovery of the blood system from immunosuppression?

Answer 9

granulocyte colony stimulating factor (G-CSF)

Question 10

this class of drugs are reactive substances that are highly toxic and may form covalent adducts with DNA bases that result in tumor cell death.

Answer 10

alkylating agents (bischloroethylamines and nitrosureas)

Question 11

this type of alkylating agent is also known as nitrogen mustard and was used in WWI as a biochemical weapon

Answer 11

bischloroethylamines (methchloethamine and the less reactive cyclophosphamide)

Question 12

these alkylating agent have the advantage of little cross-resistance with other alkylating agents, and because they can cross the blood-brain barrier may be used to treat brain tumors

Answer 12

nitrosureas

Question 13

this nitrosurea is effective against Hodgkin’s disease as a member of the MOPP regimen, but may cause secondary leukemia because it introduces point mutations (ie, leukemogenic)

Answer 13

procarbazine

Question 14

This class of chemotherapeutic agents inhibit metabolic processes essential in the S phase of the cell cycle

Answer 14

anti-tumor antimetabolites (methotrexate and various purine/pyridmidine antagonists)

Question 15

Which of the following is NOT a property of methotrexate?

A. It is a folic acid analog
B. It works by blocking the synthesis of DNA, RNA and protein precursors
C. It is an M-phase specific agent
D. It accumulates in cells as a polyglutamate derivative
E. It is a potent inhibitor of DHFR

Answer 15

C. Methotrexate is an S phase-specific drug.

Question 16

All of the following are mechanisms of resistance to methotrexate that a tumor cell may employ EXCEPT which?

A. decreased uptake of the drug
B. increased synthesis of formyl-FH4
C. DHFR gene mutation
D. amplification of the DHFR gene
E. increased drug efflux through MRP receptors

Answer 16

B. Formyl-FH4 (leucovorin) is used in conjunction with methotrexate, and is given to speed recovery from the side effects of toxicity - but this is not a tumor cell mechanism of drug resistance.

Question 17

This class of agents are analogs of naturally occurring DNA or RNA bases that are converted to NMPs and NTPs, before being fraudulently incoporated into newly synthesized strands.

Answer 17

purine and pyrimidine antagonists

Question 18

one common method of drug resistance employed by tumor cells involves downregulation of this enzyme, preventing the conversion of purine antagonists to their active form

Answer 18

HGPRT (hypoxanthine-guanine phosphoribosyl transferase)

Question 19

pyrimidine antagonist whose toxic metabolite directly inhibits thymidylate synthetase or is incorporated into newly synthesized DNA and RNA

Answer 19

5-FU (fluorouracil)

Question 20

why does leucovorin (folinic acid), when administered with fluorouracil, enhance instead of alleviate its toxicity?

Answer 20

they both bind synergistically to the same target - the active site of thymidilate synthetase

Question 21

this enzyme, found to be elevated in tumor cells, is involved in the metabolic activation of the prodrug capecitabine, which is a precursor to the pyrimidine antagonist fluorouracil

Answer 21

thymidine phosphorylase

Question 22

this pyrimidine antagonist is metabolically converted to its NTP form and incorporated into newly synthesized strands of DNA, blocking further polymerization once it is incorporated and causing breaks in the strand.

Answer 22

cytarabine

Question 23

one common method of drug resistance employed by tumor cells involves mutation of this enzyme, preventing the conversion of the pyrimidine antagonist cyatarbine to its active form

Answer 23

deoxycytidine kinase

Question 24

this class of chemotherapeutics were initially discovered as antimicrobial agents, and exert significant toxicity to tumor cells

Answer 24

anti-tumor antibiotics

Question 25

These anti-tumor antibiotics are DNA intercalating agents that bind with high affinity to DNA, interfering with replication and causing mutations and strand breaks, as well as interfering with DNA topoisomerase II function

Answer 25

anthracyclines (doxorubicin and daunorubicin)

Question 26

doxorubicin is a widely used and effective anthracycline but has what irreversible side effect at high doses?

Answer 26

cardiac toxicity

Question 27

what is the main benefit and a serious side effect of the anti-tumor antibiotic bleomycin?

Answer 27

benefit: not significnatly myelosuppressive and is therefore useful in combination regimens like ABVD for the treatment of Hodgkin’s

serious side effect: pulmonary fibrosis

Question 28

This class of chemotherapeutic agents are M-phase specific agents that interfere with mitotic spindle function by binding to tubulin subunits during mitosis

Answer 28

mitotic spindle poisons (vinca alkyloids and taxanes)

Question 29

these vinca alkyloids inhibit microtubule (tubulin) polymerization and are effective in ABVD combination regimen for the treatment of Hodgkin’s and other lymphomas

Answer 29

vinblastine and vincristine

Question 30

True or false: vinblastine and vincristine are similar in structure and function, but vinblastine has more acute side effects and is dose-limiting in neurotoxicity.

Answer 30

False. Vinblastine does have more acute side effects than vincristine but is dose-limiting in bone marrow depression, not in neurotoxicity

Question 31

this is a mitotic spindle poison that is widely used for the treatment of breast and ovarian cancer and works by binding to tubulin to block disassembly

Answer 31

paclitaxel

Question 32

these chemotherapeutics elicit DNA strand breaks and interfere with their religation

Answer 32

topoisomerase inhibitors

Question 33

True or false: Topoisomerase I inhibitors include topotecan and irinotecan which bind to the “cleavable complex” of DNA topoisomerase I, preventing religation of single strand breaks.

Answer 33

True. Remember that these inhibitors do not actually break the strand.

Question 34

Give 2 examples of DNA topoisomerase II inhibitors

Answer 34

etoposide and anthracycline antibioitics (daunorubicin and doxorubicin)

Question 35

while not truly alkylating agents, this class of chemotherapeutics form adducts with DNA bases and exert toxicity to tumor cells; may cause kidney and nerve dysfunction

Answer 35

platinum coordination complexes (just need to know cisplatin)

Question 36

_____ is a selective estrogen response modulator (SERM) that acts as both a competitive inhibitor and a partial agonist of the estrogen receptor

Answer 36

tamoxifen (or raloxifene).

Remember that raloxifene has some notable advantages over tamoxifen:

1) it is an antagonist of ER+ breast and uterine tissue, so it is a good treatment choice for breast cancer without the estrogenic effects to the endometrium
2) lower incidence of uterine cancer than tamoxifen
3) lower incidence of clotting than tamoxifen

Question 37

mammary tumors are characterized in terms of their what?

Answer 37

estrogen receptor status. ER+ mammary tumors (~40%) can be managed by estrogen antagonists with SERMs, or estrogen ablation with aromatase inhibitors

Question 38

though prohpylactic tamoxifen treatment has been suggested as an effective means of breast cancer prevention in high-risk women (~50% reduction), it is not used routinely for this purpose. why is this?

Answer 38

side effects including thrombosis/embolism and endometrial cancer; also, it has not been shown to significantly increase life span in women at risk.

Question 39

class of chemotherapeutics reserved for post-menopausal women that inhibit the conversion of androgens to estrogen

Answer 39

aromatase inhibitors (letrozole, anastrozole, exemestane)

Question 40

what advantage do aromatase inhibitors have over SERMs?

Answer 40

greatly reduces risk of breast cancer and no enhanced incidence of thrombosis or uterine cancer

Question 41

Which of these is NOT a side effect of the aromatase inhibitor exemestane?

A. increased incidence of breast cancer
B. decreased incidence of thrombosis
C. joint pain
D. loss of bone density
E. decreased incidence of uterine cancer

Answer 41

A. Exemestane greatly reduces the risk of breast cancer.

Question 42

anti-androgen therapeutic that downregulates GnRH pituitary receptors when administered in continuous, high doses (ablation therapy)

Answer 42

leuprolide

Question 43

why is the androgen receptor antagonist flutamide, when used alone, ineffective against prostate cancer?

Answer 43

the androgen receptor undergoes rapid mutation as a drug resistance mechanism of the tumor cell; you need to use this drug in conjunction with leuprolide to block the initial “flare” of prostate cancer at the start of leuprolide therapy

Question 44

corticosteroid that is used in several multidrug regimens for induction of apoptosis in leukemia cells and is useful in inducing remission in some lymphomas and myelomas

Answer 44

prednisone

Question 45

this class of therapeutics inhibit the function of activated oncogenes or proteins necessary for tumor cell proliferation and tumor angiogenesis

Answer 45

targeted agents (kinase inhibitors and antibodies)

Question 46

this target of erlotinib and cetuximab is overexpressed (mutationally activated) in various cancers: lung, brain, head and neck.

Answer 46

EGF receptor protein tyrosine kinase

Question 47

this target of lapatinib and trastuzumab is overexpressed particularly in breast cancers

Answer 47

HER2 protein tyrosine kinase

Question 48

this drug targets the activated bcr/abl protein kinase arising from gene rearrangement/fusion in chronic myelogenous leukemia

Answer 48

imatinib

Question 49

brentuximab is an antibody conjugated to a mitotic spindle poison that targets this surface antigen of some Hodgkin and non-Hodgkin lymphoma cells

Answer 49

CD30