Anticancer Drugs I

What are examples of antimetabolites?

Capecitabine, Gemcitabine, Cytarabine, 5-FU, Methotrexate, Pralatrexate

4. Q: What is the general mechanism of antimetabolites?

A: They mimic/inhibit normal DNA/RNA building blocks, disrupting nucleic acid synthesis.

5. Q: What phase of the cell cycle do antimetabolites primarily affect?

A: S phase because DNA is actively synthesized.

6. Q: What does the "-metabolite" concept mean in antimetabolites?

A: The drug resembles a normal metabolite/building block but interferes with its normal function.

7. Q: What enzyme does methotrexate inhibit?

A: Dihydrofolate reductase (DHFR).

8. Q: Why does DHFR inhibition kill rapidly dividing cells?

A: ↓ active folate → ↓ thymidine + purine synthesis → impaired DNA synthesis.

9. Q: What drug rescues normal cells from high-dose methotrexate toxicity?

A: Leucovorin (folinic acid).

10. Q: Why does leucovorin rescue methotrexate toxicity?

A: It provides active folate, bypassing DHFR inhibition.

11. Q: What are major methotrexate toxicities?

A: Myelosuppression, mucositis, hepatotoxicity, nephrotoxicity.

12. Q: How can methotrexate nephrotoxicity be reduced?

A: Hydration + urine alkalinization + leucovorin rescue.

13. Q: What class is pralatrexate?

A: Antifolate antimetabolite.

14. Q: What cancer is pralatrexate associated with?

A: T-cell lymphoma.

15. Q: What is 5-FU?

A: A pyrimidine analog antimetabolite.

16. Q: What enzyme does 5-FU inhibit?

A: Thymidylate synthase.

17. Q: What is the consequence of thymidylate synthase inhibition?

A: ↓ thymidine → impaired DNA synthesis → “thymineless death.”

18. Q: What is capecitabine?

A: An oral prodrug of 5-FU.

19. Q: Why is capecitabine relatively tumor-selective?

A: It is converted to 5-FU by enzymes that are relatively concentrated in tumor tissue.

20. Q: What is the classic toxicity of capecitabine?

A: Hand-foot syndrome ± diarrhea.

21. Q: What important interaction distinguishes leucovorin's effects on MTX vs 5-FU?

A: Leucovorin rescues MTX but enhances 5-FU.

22. Q: What type of antimetabolite is cytarabine?

A: Pyrimidine analog.

23. Q: How does cytarabine inhibit DNA synthesis?

A: Inhibits DNA polymerase and causes DNA chain termination.

24. Q: What major cancer is cytarabine used for?

A: AML.

25. Q: Why might cytarabine be given intrathecally?

A: To treat/prevent CNS/meningeal leukemia because normal systemic penetration across the BBB is poor.

26. Q: What is a characteristic toxicity of high-dose cytarabine?

A: Conjunctivitis → steroid eye drops can prevent it.

27. Q: What type of drug is gemcitabine?

A: Pyrimidine analog antimetabolite.

28. Q: What cancers are strongly associated with gemcitabine?

A: Pancreatic cancer and NSCLC.

29. Q: What important property does gemcitabine have?

A: It is a potent radiosensitizer.

30. Q: Why are some anticancer drugs called antitumor antibiotics?

A: They were originally derived from microorganisms, particularly Streptomyces, and have antitumor rather than antibacterial effects.

31. Q: What is the mechanism of bleomycin?

A: Binds iron → generates free radicals → DNA strand breaks.

32. Q: What phase is bleomycin most associated with?

A: G2 phase.

33. Q: What is the signature toxicity of bleomycin?

A: Pulmonary fibrosis.

34. Q: Why does bleomycin cause relatively little myelosuppression?

A: Bone marrow has relatively more of the enzyme that inactivates bleomycin; lungs and skin are more vulnerable.

35. Q: What cancers commonly use bleomycin?

A: Hodgkin lymphoma and testicular cancer.

36. Q: What class does daunorubicin belong to?

A: Anthracycline antitumor antibiotic.

37. Q: What are the 3 major mechanisms of anthracyclines?

A: DNA intercalation + Topoisomerase II inhibition + free-radical formation.

38. Q: What is the major toxicity of daunorubicin?

A: Dose-dependent cardiotoxicity.

39. Q: Why do anthracyclines cause cardiotoxicity?

A: Free-radical damage to cardiac muscle.

40. Q: What happens to anthracycline cardiotoxicity with cumulative exposure?

A: Risk increases with cumulative lifetime dose and can lead to heart failure.

what are the alkylatinf/adducting agents?

Busulfan, Carboplatin, Cisplatin

41. Q: What is the general mechanism of alkylating/adducting agents?

A: Covalently modify DNA, especially guanine, causing DNA damage/cross-linking.

42. Q: Are alkylating agents cell-cycle specific?

A: No — cell-cycle nonspecific.

43. Q: What class is busulfan?

A: Alkylating agent.

44. Q: What is the signature toxicity of busulfan?

A: Pulmonary fibrosis ("busulfan lung").

45. Q: What major hematologic malignancy is associated with busulfan?

A: CML.

46. Q: Are platinum drugs technically alkylating agents?

A: No, but they are alkylating-like/adducting agents because they create DNA cross-links.

47. Q: How does cisplatin damage DNA?

A: Platinum binds guanine → DNA cross-links → impaired replication/transcription.

48. Q: What are the 3 classic toxicities of cisplatin?

A: Nephrotoxicity + ototoxicity + severe nausea/vomiting.

49. Q: How do you reduce cisplatin nephrotoxicity?

A: Aggressive IV hydration.

50. Q: What type of hearing loss is associated with cisplatin?

A: High-frequency sensorineural hearing loss.

51. Q: What is the major toxicity of carboplatin?

A: Myelosuppression.

52. Q: How does carboplatin generally compare with cisplatin?

A: Less nephrotoxic/ototoxic, but more myelosuppressive.

what are the BBB drugs?

A: It prevents many systemic drugs from adequately entering the CNS, creating a pharmacologic sanctuary.

54. Q: What characteristic allows certain anticancer drugs to cross the BBB?

A: High lipid solubility.

55. Q: Which professor-listed drugs readily cross the BBB?

A: Carmustine, lomustine, temozolomide.

56. Q: What class are carmustine and lomustine?

A: Nitrosoureas.

57. Q: Why are nitrosoureas useful for brain tumors?

A: They are lipid-soluble and cross the BBB.

58. Q: What are important toxicities of nitrosoureas?

A: Myelosuppression + pulmonary toxicity.

59. Q: Why is temozolomide important for CNS tumors?

A: It crosses the BBB and is used for glioblastoma.

60. Q: What is the mechanism of temozolomide?

A: Methylates DNA, particularly guanine → DNA damage.

61. Q: What cell-cycle phase do vinca alkaloids target?

A: M phase.

62. Q: How do vinca alkaloids affect microtubules?

A: Bind tubulin and prevent microtubule polymerization.

63. Q: What happens to the cell when vinca alkaloids disrupt microtubules?

A: Mitotic spindle cannot form properly → cell is arrested in metaphase → cell death.

64. Q: What is the signature toxicity of vincristine?

A: Peripheral neuropathy.

65. Q: What GI toxicity is associated with vincristine?

A: Constipation.

66. Q: What is the critical administration warning for vincristine?

A: Never administer intrathecally — fatal.

67. Q: Why does vincristine cause relatively little myelosuppression?

A: Compared with other vinca alkaloids, it is more neurotoxic and less myelosuppressive.

68. Q: What is the major toxicity distinguishing vinblastine from vincristine?

A: More myelosuppression.

69. Q: What is a classic combination containing vinblastine?

A: Bleomycin + vinblastine + cisplatin for testicular cancer.

what are the estrogen receptor modulators?

Raloxifene, Tamoxifen

70. Q: What does SERM stand for?

A: Selective Estrogen Receptor Modulator.

71. Q: How do SERMs work?

A: Bind estrogen receptors but act as antagonists in some tissues and agonists in others.

72. Q: What is tamoxifen's effect in breast tissue?

A: Estrogen receptor antagonist → inhibits estrogen-driven tumor growth.

73. Q: What is the major uterine effect of tamoxifen?

A: Partial estrogen agonist in endometrium.

74. Q: What major cancer risk does tamoxifen increase?

A: Endometrial cancer.

75. Q: What other major adverse effect should you know for tamoxifen?

A: Venous thromboembolism.

76. Q: What are common symptoms caused by tamoxifen's hormonal effects?

A: Hot flashes.

77. Q: How does raloxifene differ from tamoxifen in the uterus?

A: Raloxifene is an estrogen antagonist in the uterus, so it does not increase endometrial cancer risk.

78. Q: What is the easiest exam distinction?

A: Tamoxifen → ↑ endometrial cancer; raloxifene → no increased endometrial cancer risk.

what are the aromatase inhibitors?

Anastrozole, Letrozole, Exemestane

79. Q: What enzyme do aromatase inhibitors block?

A: Aromatase.

80. Q: What does aromatase normally do?

A: Converts androgens → estrogens in peripheral tissues.

81. Q: Why are aromatase inhibitors especially useful after menopause?

A: Peripheral tissues become the major source of estrogen after ovarian estrogen production declines.

82. Q: What are the professor-listed aromatase inhibitors?

A: Anastrozole, letrozole, exemestane.

83. Q: What are important adverse effects of aromatase inhibitors?

A: Arthralgia + bone loss/osteoporosis.

what are the immune check point inhibitors?

Pembrolizumab, Nivolumab

84. Q: What is the basic purpose of immune checkpoints?

A: They act as brakes on T-cell activation to prevent excessive immune responses.

85. Q: What do pembrolizumab and nivolumab block?

A: PD-1 on T cells.

86. Q: What happens when PD-1 is blocked?

A: T-cell inhibition is removed → T cells can attack tumor cells.

87. Q: Why can checkpoint inhibitors cause autoimmune-type toxicity?

A: Removing immune brakes can cause T cells to attack normal tissues.

88. Q: What are high-yield immune-related adverse effects?

A: Colitis, pneumonitis, hepatitis, nephritis, thyroid dysfunction, skin rash.

89. Q: How are severe immune checkpoint toxicities treated?

A: Corticosteroids/immunosuppression.

90. Q: A patient on nivolumab develops severe diarrhea. What should you suspect?

A: Immune-mediated colitis from checkpoint inhibition.

what are the microtubule inhibitors?

paclitaxel

91. Q: What does paclitaxel target?

A: Tubulin/microtubules.

92. Q: How does paclitaxel affect microtubules?

A: Promotes polymerization and prevents depolymerization.

93. Q: What phase does paclitaxel primarily affect?

A: M phase.

94. Q: How do taxanes differ from vinca alkaloids?

A:

• Vinca: prevent microtubule assembly.

• Taxanes: prevent microtubule disassembly.

95. Q: What are major paclitaxel toxicities?

A: Neutropenia, peripheral neuropathy, hypersensitivity reactions.

96. Q: How are paclitaxel hypersensitivity reactions prevented?

A: Premedicate with corticosteroid + antihistamine + H2 blocker.

what are the topoisomerase inhibitors?

Etoposide, Irinotecan, Topotecan