MCQ Quiz: Pharmacology of Anticancer Therapeutics

Welcome, PharmD students, to this focused MCQ quiz on the Pharmacology of Anticancer Therapeutics! Understanding the diverse mechanisms by which anticancer drugs exert their effects is crucial for effective and safe oncology pharmacy practice. This quiz will delve into the pharmacology of various classes, including traditional cytotoxic agents, modern targeted therapies, and cutting-edge immunotherapies. We’ll explore their molecular targets, mechanisms of action, pathways to resistance, and the pharmacological basis for their therapeutic use and toxicities. Let’s test your knowledge!

1. Alkylating agents, such as cyclophosphamide and cisplatin, primarily exert their cytotoxic effect by:

• a) Inhibiting microtubule formation.
• b) Forming covalent bonds with DNA, leading to cross-linking, strand breaks, and interference with DNA replication and transcription.
• c) Blocking estrogen receptors.
• d) Inhibiting tyrosine kinases.

Answer: b) Forming covalent bonds with DNA, leading to cross-linking, strand breaks, and interference with DNA replication and transcription.

2. Antimetabolites, like methotrexate and 5-fluorouracil, are generally cell cycle-specific, primarily acting during which phase of the cell cycle?

• a) G0 phase (resting phase)
• b) M phase (mitosis)
• c) S phase (DNA synthesis)
• d) G2 phase (pre-mitotic phase)

Answer: c) S phase (DNA synthesis)

3. Methotrexate, a folate analog, inhibits which enzyme, thereby interfering with DNA synthesis?

• a) Thymidylate synthase
• b) Dihydrofolate reductase (DHFR)
• c) DNA polymerase
• d) Topoisomerase I

Answer: b) Dihydrofolate reductase (DHFR)

4. Anthracyclines, such as doxorubicin and daunorubicin, are antitumor antibiotics that have multiple proposed mechanisms of action, including:

• a) Only inhibition of microtubule assembly.
• b) Intercalation into DNA, inhibition of topoisomerase II, and generation of free radicals.
• c) Selective inhibition of bacterial cell wall synthesis.
• d) Activation of estrogen receptors.

Answer: b) Intercalation into DNA, inhibition of topoisomerase II, and generation of free radicals.

5. Vinca alkaloids (e.g., vincristine, vinblastine) target which cellular structures, leading to M-phase arrest?

• a) DNA
• b) Ribosomes
• c) Microtubules (by inhibiting tubulin polymerization)
• d) Mitochondria

Answer: c) Microtubules (by inhibiting tubulin polymerization)

6. Taxanes (e.g., paclitaxel, docetaxel) also target microtubules but have a different mechanism than vinca alkaloids. Taxanes work by:

• a) Inhibiting tubulin polymerization.
• b) Promoting microtubule assembly and stabilizing existing microtubules, thereby preventing their disassembly and causing M-phase arrest.
• c) Directly damaging DNA.
• d) Blocking folic acid metabolism.

Answer: b) Promoting microtubulo e assembly and stabilizing existing microtubules, thereby preventing their disassembly and causing M-phase arrest.

7. Topoisomerase inhibitors (e.g., etoposide, irinotecan) cause cancer cell death by:

• a) Preventing the formation of the mitotic spindle.
• b) Interfering with the enzymes that manage DNA supercoiling and untangling during replication and transcription, leading to DNA strand breaks.
• c) Blocking growth factor receptors on the cell surface.
• d) Inhibiting protein synthesis.

Answer: b) Interfering with the enzymes that manage DNA supercoiling and untangling during replication and transcription, leading to DNA strand breaks.

8. Imatinib (Gleevec) is a small molecule inhibitor that revolutionized the treatment of chronic myeloid leukemia (CML) by selectively targeting:

• a) The estrogen receptor.
• b) The BCR-ABL tyrosine kinase, an abnormal protein driving CML cell proliferation.
• c) DNA polymerase.
• d) Microtubules.

Answer: b) The BCR-ABL tyrosine kinase, an abnormal protein driving CML cell proliferation.

9. Monoclonal antibodies (mAbs) ending in “-mab” (e.g., trastuzumab, rituximab) are a form of targeted therapy. Trastuzumab (Herceptin) targets which protein overexpressed in some breast cancers?

• a) Vascular Endothelial Growth Factor (VEGF)
• b) Epidermal Growth Factor Receptor (EGFR)
• c) Human Epidermal growth factor Receptor 2 (HER2)
• d) CD20 antigen

Answer: c) Human Epidermal growth factor Receptor 2 (HER2)

10. Rituximab is a monoclonal antibody that targets the CD20 antigen found on the surface of:

• a) Normal and malignant B lymphocytes, used in treating certain lymphomas and autoimmune diseases.
• b) T lymphocytes.
• c) Myeloid cells.
• d) Epithelial cancer cells.

Answer: a) Normal and malignant B lymphocytes, used in treating certain lymphomas and autoimmune diseases.

11. Immune checkpoint inhibitors, such as pembrolizumab (anti-PD-1) or ipilimumab (anti-CTLA-4), work by:

• a) Directly stimulating cancer cell apoptosis.
• b) Blocking inhibitory pathways (checkpoints) on immune cells (like T cells), thereby enhancing the anti-tumor immune response.
• c) Inhibiting tumor angiogenesis.
• d) Alkylating cancer cell DNA.

Answer: b) Blocking inhibitory pathways (checkpoints) on immune cells (like T cells), thereby enhancing the anti-tumor immune response.

12. Tamoxifen, used in ER-positive breast cancer, is a Selective Estrogen Receptor Modulator (SERM). Its primary pharmacological action in breast tissue is:

• a) To increase estrogen production.
• b) To act as an estrogen antagonist, blocking estrogen binding to its receptor and inhibiting tumor growth.
• c) To directly damage DNA.
• d) To inhibit aromatase enzyme.

Answer: b) To act as an estrogen antagonist, blocking estrogen binding to its receptor and inhibiting tumor growth.

13. Aromatase inhibitors (e.g., anastrozole, letrozole) are used in postmenopausal women with ER-positive breast cancer. Their mechanism involves:

• a) Blocking the estrogen receptor directly.
• b) Inhibiting the enzyme aromatase, which is responsible for converting androgens to estrogens in peripheral tissues.
• c) Stimulating progesterone production.
• d) Inhibiting DNA synthesis.

Answer: b) Inhibiting the enzyme aromatase, which is responsible for converting androgens to estrogens in peripheral tissues.

14. A common mechanism of resistance to alkylating agents involves:

• a) Decreased expression of target receptors.
• b) Increased activity of DNA repair mechanisms in cancer cells.
• c) Upregulation of microtubule production.
• d) Decreased drug efflux from cancer cells.

Answer: b) Increased activity of DNA repair mechanisms in cancer cells.

15. The pharmacology of 5-Fluorouracil (5-FU) involves its conversion to metabolites that inhibit _______, thereby interfering with DNA synthesis.

• a) Dihydrofolate reductase
• b) Thymidylate synthase
• c) Topoisomerase II
• d) BCR-ABL tyrosine kinase

Answer: b) Thymidylate synthase

16. A major dose-limiting toxicity associated with anthracyclines like doxorubicin is:

• a) Peripheral neuropathy.
• b) Cardiotoxicity (acute and chronic).
• c) Severe nephrotoxicity.
• d) Pulmonary fibrosis.

Answer: b) Cardiotoxicity (acute and chronic).

17. Bevacizumab (Avastin) is a monoclonal antibody that targets:

• a) HER2
• b) CD20
• c) Vascular Endothelial Growth Factor (VEGF), thereby inhibiting angiogenesis (new blood vessel formation).
• d) PD-1

Answer: c) Vascular Endothelial Growth Factor (VEGF), thereby inhibiting angiogenesis (new blood vessel formation).

18. The pharmacology of EGFR inhibitors (e.g., cetuximab, erlotinib) is based on blocking signaling pathways that promote:

• a) Immune cell activation.
• b) Cancer cell proliferation, survival, and metastasis.
• c) Apoptosis of normal cells.
• d) DNA repair.

Answer: b) Cancer cell proliferation, survival, and metastasis.

19. Immune-related adverse events (irAEs) are a distinct class of toxicities associated with immunotherapy, which can affect various organ systems due to:

• a) Direct cytotoxic effects on normal tissues.
• b) Widespread immune system activation that can lead to inflammatory reactions in normal tissues.
• c) Inhibition of DNA synthesis in healthy cells.
• d) Suppression of the bone marrow.

Answer: b) Widespread immune system activation that can lead to inflammatory reactions in normal tissues.

20. Cell cycle-non-specific (CCNS) chemotherapeutic agents can kill cancer cells:

• a) Only during the S phase.
• b) Only during the M phase.
• c) At any phase of the cell cycle, including G0 (resting phase).
• d) Only if they are rapidly dividing.

Answer: c) At any phase of the cell cycle, including G0 (resting phase).

21. From a medicinal chemistry perspective, cisplatin and other platinum-based compounds are alkylating-like agents that form _______ with DNA.

• a) Hydrogen bonds
• b) Ionic bonds
• c) Covalent intra-strand and inter-strand cross-links
• d) Van der Waals interactions

Answer: c) Covalent intra-strand and inter-strand cross-links

22. Leucovorin (folinic acid) is often administered with methotrexate to:

• a) Enhance the cytotoxic effect of methotrexate on cancer cells.
• b) “Rescue” normal cells from the toxic effects of methotrexate by bypassing DHFR inhibition and providing a source of reduced folates.
• c) Increase the renal excretion of methotrexate.
• d) Prevent methotrexate-induced nausea.

Answer: b) “Rescue” normal cells from the toxic effects of methotrexate by bypassing DHFR inhibition and providing a source of reduced folates.

23. The pharmacology of bleomycin, an antitumor antibiotic, includes causing DNA strand breaks through:

• a) Inhibition of topoisomerase I.
• b) Alkylation of guanine bases.
• c) Generation of free radicals that oxidize DNA, often requiring iron as a cofactor.
• d) Microtubule stabilization.

Answer: c) Generation of free radicals that oxidize DNA, often requiring iron as a cofactor.

24. A common mechanism of resistance to targeted therapies like tyrosine kinase inhibitors is:

• a) Increased expression of the target protein.
• b) Decreased drug efflux.
• c) Mutations in the target kinase that prevent drug binding or activation of alternative signaling pathways.
• d) Enhanced DNA repair.

Answer: c) Mutations in the target kinase that prevent drug binding or activation of alternative signaling pathways.

25. Which of the following is a key pharmacological consideration for monoclonal antibodies?

• a) They are usually small molecules with excellent oral bioavailability.
• b) They are large proteins typically administered intravenously and can have long half-lives.
• c) They primarily target intracellular enzymes.
• d) They rarely cause infusion-related reactions.

Answer: b) They are large proteins typically administered intravenously and can have long half-lives.

26. Antiandrogen therapy for prostate cancer, using drugs like bicalutamide, works by:

• a) Increasing testosterone production.
• b) Blocking the binding of androgens (like testosterone and DHT) to the androgen receptor.
• c) Inhibiting aromatase.
• d) Directly lysing prostate cancer cells.

Answer: b) Blocking the binding of androgens (like testosterone and DHT) to the androgen receptor.

27. The primary pharmacological target of etoposide is:

• a) Microtubules
• b) DNA alkylation
• c) Topoisomerase II, leading to DNA strand breaks.
• d) Dihydrofolate reductase.

Answer: c) Topoisomerase II, leading to DNA strand breaks.

28. From a medicinal chemistry point of view, many small molecule kinase inhibitors are designed to:

• a) Bind to the DNA major groove.
• b) Compete with ATP for its binding site on the kinase or bind to an allosteric site.
• c_ Intercalate between DNA base pairs.
• d) Form free radicals.

Answer: b) Compete with ATP for its binding site on the kinase or bind to an allosteric site.

29. A potential pharmacological consequence of inhibiting VEGF (e.g., with bevacizumab) is:

• a) Enhanced tumor growth.
• b) Impaired wound healing and risk of hypertension or bleeding, due to effects on normal angiogenesis and vascular function.
• c) Severe myelosuppression.
• d) Cardiotoxicity similar to anthracyclines.

Answer: b) Impaired wound healing and risk of hypertension or bleeding, due to effects on normal angiogenesis and vascular function.

30. The pharmacology of bortezomib, a proteasome inhibitor used in multiple myeloma, involves:

• a) Inhibiting DNA replication.
• b) Blocking the degradation of ubiquitinated proteins by the proteasome, leading to accumulation of regulatory proteins and apoptosis.
• c) Inhibiting angiogenesis.
• d) Activating T-cells.

Answer: b) Blocking the degradation of ubiquitinated proteins by the proteasome, leading to accumulation of regulatory proteins and apoptosis.

31. Cyclophosphamide is a prodrug that requires metabolic activation in the _______ to form its active alkylating metabolites.

• a) Kidneys
• b) Lungs
• c) Liver (by CYP450 enzymes)
• d) Bone marrow

Answer: c) Liver (by CYP450 enzymes)

32. The pharmacology of irinotecan involves its conversion to an active metabolite, SN-38, which inhibits:

• a) Topoisomerase II
• b) Topoisomerase I
• c) Microtubule polymerization
• d) Dihydrofolate reductase

Answer: b) Topoisomerase I

33. A key pharmacological challenge with many cytotoxic anticancer drugs is their lack of selectivity, leading to toxicity in:

• a) Only cancer cells.
• b) Normal, rapidly dividing cells (e.g., bone marrow, GI mucosa, hair follicles).
• c) Only quiescent (G0) cells.
• d) Only neuronal tissue.

Answer: b) Normal, rapidly dividing cells (e.g., bone marrow, GI mucosa, hair follicles).

34. Gonadotropin-releasing hormone (GnRH) agonists (e.g., leuprolide) used for prostate cancer initially cause a surge in testosterone, followed by _______ due to receptor downregulation.

• a) sustained high testosterone levels
• b) a profound decrease in testosterone production (medical castration)
• c) increased estrogen levels
• d) no change in testosterone

Answer: b) a profound decrease in testosterone production (medical castration)

35. The medicinal chemistry of monoclonal antibodies often involves “humanizing” them or creating fully human antibodies to:

• a) Increase their antigenicity and immune reactions.
• b) Reduce their immunogenicity (risk of human anti-mouse antibody – HAMA – reactions) and prolong their half-life.
• c) Make them orally bioavailable.
• d) Decrease their binding affinity to the target.

Answer: b) Reduce their immunogenicity (risk of human anti-mouse antibody – HAMA – reactions) and prolong their half-life.

36. A common pharmacological effect of many anticancer drugs that damage DNA is the induction of:

• a) Cell proliferation.
• b) Apoptosis (programmed cell death) in cancer cells.
• c) Angiogenesis.
• d) Hormone production.

Answer: b) Apoptosis (programmed cell death) in cancer cells.

37. Which of the following is a key principle in overcoming drug resistance in cancer chemotherapy?

• a) Using single agents at very low doses.
• b) Using combination chemotherapy with drugs that have different mechanisms of action and non-overlapping toxicities.
• c) Discontinuing therapy as soon as minimal response is seen.
• d) Administering all chemotherapy agents orally.

Answer: b) Using combination chemotherapy with drugs that have different mechanisms of action and non-overlapping toxicities.

38. The pharmacology of immune checkpoint inhibitors like anti-PD-1 antibodies involves enhancing T-cell activity. This can lead to what type of characteristic side effects?

• a) Only myelosuppression.
• b) Immune-related adverse events (irAEs) such as colitis, dermatitis, hepatitis, endocrinopathies.
• c) Severe nephrotoxicity as the primary concern.
• d) Only infusion reactions.

Answer: b) Immune-related adverse events (irAEs) such as colitis, dermatitis, hepatitis, endocrinopathies.

39. From a medicinal chemistry perspective, small molecule tyrosine kinase inhibitors (TKIs) are typically designed to be:

• a) Large proteins administered IV.
• b) Orally bioavailable compounds that can penetrate cell membranes to reach intracellular kinases.
• c) Non-specific inhibitors of all cellular kinases.
• d) Unable to cross the blood-brain barrier.

Answer: b) Orally bioavailable compounds that can penetrate cell membranes to reach intracellular kinases.

40. The pharmacology of drugs targeting tumor angiogenesis aims to:

• a) Increase the blood supply to the tumor.
• b) Inhibit the formation of new blood vessels that tumors need to grow and metastasize.
• c) Directly kill tumor cells by DNA damage.
• d) Stimulate the patient’s immune system.

Answer: b) Inhibit the formation of new blood vessels that tumors need to grow and metastasize.

41. What is the pharmacological basis for testing tumors for specific genetic mutations (e.g., EGFR mutations, ALK rearrangements) before initiating certain targeted therapies?

• a) These mutations make the tumor resistant to all forms of treatment.
• b) These therapies are only effective in tumors that harbor the specific molecular target or activating mutation.
• c) All cancer patients have the same genetic mutations.
• d) It is primarily for research and does not guide treatment.

Answer: b) These therapies are only effective in tumors that harbor the specific molecular target or activating mutation.

42. The pharmacology of antimetabolites often depends on their structural similarity to:

• a) Natural hormones.
• b) Endogenous nucleosides, purines, or pyrimidines, allowing them to interfere with nucleic acid synthesis.
• c) Microtubule proteins.
• d) Growth factors.

Answer: b) Endogenous nucleosides, purines, or pyrimidines, allowing them to interfere with nucleic acid synthesis.

43. A common adverse effect related to the pharmacology of vinca alkaloids is:

• a) Severe cardiotoxicity.
• b) Peripheral neuropathy (neurotoxicity).
• c) Hemorrhagic cystitis.
• d) Pulmonary fibrosis.

Answer: b) Peripheral neuropathy (neurotoxicity).

44. Medicinal chemistry approaches to improve the therapeutic index of anticancer drugs include:

• a) Increasing their non-specific cytotoxicity.
• b) Developing targeted delivery systems or prodrugs that are selectively activated in tumor tissue.
• c) Making them more resistant to metabolism.
• d) Broadening their mechanism of action to affect more cellular processes.

Answer: b) Developing targeted delivery systems or prodrugs that are selectively activated in tumor tissue.

45. The pharmacology of cancer immunotherapy can sometimes lead to a phenomenon called “pseudoprogression,” where:

• a) The tumor rapidly shrinks and disappears.
• b) The tumor initially appears to grow or new lesions appear due to immune cell infiltration, before actual tumor regression occurs.
• c) The patient develops severe, irreversible autoimmune disease.
• d) The immunotherapy has no effect.

Answer: b) The tumor initially appears to grow or new lesions appear due to immune cell infiltration, before actual tumor regression occurs.

46. Which type of anticancer therapeutic often requires monitoring for infusion-related reactions (IRRs) during or shortly after administration?

• a) Oral small molecule inhibitors
• b) Monoclonal antibodies
• c) Oral hormonal agents
• d) Subcutaneous G-CSF injections

Answer: b) Monoclonal antibodies

47. From a pharmacological perspective, the Log-Kill Hypothesis in cancer chemotherapy suggests that:

• a) A given dose of chemotherapy kills a constant number of cancer cells.
• b) A given dose of chemotherapy kills a constant fraction (percentage) of cancer cells, not a constant number.
• c) Cancer cells are immortal.
• d) Chemotherapy only makes cancer cells dormant.

Answer: b) A given dose of chemotherapy kills a constant fraction (percentage) of cancer cells, not a constant number.

48. The development of antibody-drug conjugates (ADCs) is a medicinal chemistry strategy that combines:

• a) Two different small molecule inhibitors.
• b) A monoclonal antibody (for targeting) with a potent cytotoxic payload (drug).
• c) An immunotherapy agent with a hormonal agent.
• d) A chemotherapy drug with a vitamin.

Answer: b) A monoclonal antibody (for targeting) with a potent cytotoxic payload (drug).

49. Understanding the specific pharmacological targets of anticancer drugs is essential for:

• a) Predicting the color of the resulting infusion.
• b) Identifying potential mechanisms of resistance and designing rational combination therapies.
• c) Calculating the patient’s body surface area.
• d) Ensuring the drug is administered at room temperature.

Answer: b) Identifying potential mechanisms of resistance and designing rational combination therapies.

50. The pharmacology of many targeted therapies depends on the principle of “oncogene addiction,” where cancer cells:

• a) Are resistant to all targeted drugs.
• b) Become highly dependent on a single activated oncogenic pathway for their proliferation and survival, making them vulnerable to its inhibition.
• c) Can switch their oncogenic drivers easily.
• d) Do not rely on any specific signaling pathways.

Answer: b) Become highly dependent on a single activated oncogenic pathway for their proliferation and survival, making them vulnerable to its inhibition.