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)?
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They cross-link DNA strands, preventing replication and transcription.- What is the major dose-limiting toxicity of cyclophosphamide and ifosfamide?
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Hemorrhagic cystitis, due to the toxic metabolite acrolein.- What drug is given to prevent hemorrhagic cystitis from cyclophosphamide?
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Mesna, which binds and inactivates acrolein in the bladder.- What is the major toxicity associated with busulfan?
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Pulmonary fibrosis- What is the mechanism of action of cisplatin and carboplatin?
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They cross-link DNA by binding platinum to DNA bases, similar to alkylating agents.- What are the two major toxicities of cisplatin?
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Nephrotoxicity and ototoxicity- What is the mechanism of action of methotrexate?
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It inhibits dihydrofolate reductase, blocking synthesis of purines, pyrimidines, and thymidylate.- What drug is given to rescue normal cells from methotrexate toxicity?
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Leucovorin (folinic acid)- What is the mechanism of action of 5-fluorouracil?
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It inhibits thymidylate synthase, blocking dTMP and DNA synthesis.- Why should 6-mercaptopurine be dose-reduced when given with allopurinol?
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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?
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Acute myeloid leukemia (and other leukemias/lymphomas)- What is the mechanism of action of vincristine and vinblastine?
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They bind tubulin and inhibit its polymerization into microtubules, blocking mitotic spindle formation.- What is the major dose-limiting toxicity of vincristine?
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Peripheral neuropathy- What is the mechanism of action of paclitaxel?
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It hyperstabilizes microtubules, preventing their disassembly and blocking mitosis.- What is the mechanism of action of doxorubicin, an anthracycline?
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It intercalates into DNA and generates free radicals, causing DNA strand breaks.
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