Chemotherapy drug classes and their mechanisms and toxicities, plus classic oncogenes and tumor suppressor gene mutations tested on USMLE Step 1.
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- What is the mechanism of action of alkylating chemotherapy agents (e.g., cyclophosphamide, busulfan)?
- They cross-link DNA strands, preventing replication and transcription.
- What is the major dose-limiting toxicity of cyclophosphamide and ifosfamide?
- Hemorrhagic cystitis, due to the toxic metabolite acrolein.
- What drug is given to prevent hemorrhagic cystitis from cyclophosphamide?
- Mesna, which binds and inactivates acrolein in the bladder.
- What is the major toxicity associated with busulfan?
- Pulmonary fibrosis
- What is the mechanism of action of cisplatin and carboplatin?
- They cross-link DNA by binding platinum to DNA bases, similar to alkylating agents.
- What are the two major toxicities of cisplatin?
- Nephrotoxicity and ototoxicity
- What is the mechanism of action of methotrexate?
- It inhibits dihydrofolate reductase, blocking synthesis of purines, pyrimidines, and thymidylate.
- What drug is given to rescue normal cells from methotrexate toxicity?
- Leucovorin (folinic acid)
- What is the mechanism of action of 5-fluorouracil?
- It inhibits thymidylate synthase, blocking dTMP and DNA synthesis.
- Why should 6-mercaptopurine be dose-reduced when given with allopurinol?
- 6-MP is normally inactivated by xanthine oxidase, which allopurinol inhibits, increasing 6-MP toxicity.
- Cytarabine is a pyrimidine antagonist mainly used to treat which type of cancer?
- Acute myeloid leukemia (and other leukemias/lymphomas)
- What is the mechanism of action of vincristine and vinblastine?
- They bind tubulin and inhibit its polymerization into microtubules, blocking mitotic spindle formation.
- What is the major dose-limiting toxicity of vincristine?
- Peripheral neuropathy
- What is the mechanism of action of paclitaxel?
- It hyperstabilizes microtubules, preventing their disassembly and blocking mitosis.
- What is the mechanism of action of doxorubicin, an anthracycline?
- It intercalates into DNA and generates free radicals, causing DNA strand breaks.