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Classification of Anticancer Agents Based on Cell Cycle Mechanism

1. Cell Cycle-Specific Drugs

Drugs Acting During the S-phase

  • Antimetabolites: Methotrexate, 5-fluorouracil (5-FU), Cytarabine
  • Mechanism of Action: Inhibit DNA synthesis by interfering with folate metabolism or incorporating false metabolites into DNA.
  • Therapeutic Uses: Leukemia, lymphoma, breast cancer, solid tumors.
  • Adverse Side Effects: Myelosuppression, mucositis, nausea, vomiting.
  • Contraindications: Pregnancy (teratogenic), renal impairment.
  • Drug-Drug Interactions: Inhibition of renal tubular secretion by methotrexate.

Drugs Acting During the M-phase

  • Vinca Alkaloids: Vincristine, Vinblastine
  • Mechanism of Action: Bind to tubulin and inhibit microtubule formation, leading to mitotic arrest.
  • Therapeutic Uses: Leukemia, lymphomas, solid tumors.
  • Adverse Side Effects: Neuropathy, bone marrow suppression.
  • Contraindications: Liver dysfunction, peripheral neuropathy.
  • Drug-Drug Interactions: Potentiated effect when used with other myelosuppressive drugs.

2. Cell Cycle-Nonspecific Drugs

Alkylating Agents

  • Cyclophosphamide, Ifosfamide, Busulfan
  • Mechanism of Action: Form covalent bonds with DNA, causing cross-linking and strand breaks.
  • Therapeutic Uses: Leukemia, lymphoma, breast cancer, solid tumors.
  • Adverse Side Effects: Myelosuppression, alopecia, nausea, hemorrhagic cystitis (cyclophosphamide).
  • Contraindications: Pregnancy, bone marrow suppression.
  • Drug-Drug Interactions: Enhanced toxicity with other cytotoxic drugs and radiation.

3. Hormonal Agents

Estrogen Receptor Antagonists

  • Tamoxifen
  • Mechanism of Action: Blocks estrogen receptors on tumor cells, inhibiting cell proliferation.
  • Therapeutic Uses: Estrogen receptor-positive breast cancer.
  • Adverse Side Effects: Hot flashes, thromboembolic events, endometrial cancer.
  • Contraindications: Pregnancy, history of thromboembolism.
  • Drug-Drug Interactions: Increased risk of thromboembolic events with anticoagulants.

4. Targeted Therapies

Tyrosine Kinase Inhibitors

  • Imatinib
  • Mechanism of Action: Inhibit BCR-ABL fusion protein in chronic myelogenous leukemia (CML).
  • Therapeutic Uses: Chronic myelogenous leukemia (CML).
  • Adverse Side Effects: Fluid retention, nausea, vomiting, myelosuppression.
  • Contraindications: Severe liver disease.
  • Drug-Drug Interactions: Inhibited by CYP3A4 inhibitors (e.g., ketoconazole).