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Updated: Mar 9 2019

Cancer Drugs Overview

  • Definitions and Concepts
    • Growth fraction
      • high growth fraction means large percentage of cells are actively dividing
      • cytotoxic drugs are more deadly against
        • high growth fraction tumors
          • leukemias
          • lymphomas
        • normal cells with high growth fraction
          • bone marrow
          • GI
    • Cell-cycle specificity
      • cell-cycle specific drugs
        • act only during certain phases of the cell cycle
        • more effective against high-growth fraction tumors
      • cell-cycle nonspecific drugs
        • used in both high- and low-growth fraction tumors
    • Log-kill hypothesis
      • cytotoxic drugs kill a fixed percentage of tumor cells
        • not a fixed number
  • Cell Cycle
    • S phase
      • agents binding to DNA
        • alkylating agents
        • anti-tumor antibiotics
        • platinum compounds
      • antimetabolites
        • methotrexate
        • azathioprine
        • 6-MP
        • 5-FU
    • M phase
      • microtubule inhibitors
        • vinca alkaloids
        • paclitaxel
  • Sites of Action
      • Sites of Action
      • Mechanism of Action
      • Drugs
      • Mechanism
      • Nucleotide synthesis
      • Methotrexate
      • 5-FU
      • ↓ thymidine synthesis
      • 6-MP
      • ↓ purine synthesis
      • DNA
      • Alkylating agentsCisplatin
      • Cross-link DNA
      • Dactinomycin
      • Doxorubicin
      • Intercalate DNA
      • Etoposide
      • Inhibit topoisomerase II
      • Cellular division
      • Vinca alkaloids
      • Inhibit MT formation
      • Paclitaxel
      • Inhibit MT disassembly
  • Important Toxicities
      • Important Toxicities
      • Drugs
      • Toxicities
      • Bleomycin
      • Pulmonary fibrosis
      • Cisplatin and Carboplatin
      • Acoustic nerve damage and nephrotoxicity
      • Cyclophosphamide
      • Hemorrhagic cystitis
      • Doxorubicin
      • Cardiotoxicity
      • Methotrexate, 5-FU, and 6-MP
      • Myelosuppression
      • Vincristine
      • Peripheral neuropathy
  • Development of resistance
    • Tumors can develop resistance to anticancer drugs through a variety of mechanisms
      • ↓ sensitivity/affinity
        • etoposide
        • methotrexate
        • vinblastine and vincristine
      • ↓ accumulation
        • methotrexate
        • alkylating agents
        • dactinomycin
      • ↑ drug-inactivating enzymes
        • antimetabolites of purine and pyrimidine
      • ↑ trapping of drug
        • alkylating agents
        • bleomycin
        • cisplatin
        • doxorubicin
      • ↑ DNA repair
        • alkylating agents
        • cisplatin
      • ↓ bioactivation
        • antimetabolites of purine and pyrimidine
    • Combination drug regimens prevent the development of resistance
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