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Chemotherapy Overview Lecture

Chemotherapy Overview

  • Definition: A type of cancer drug treatment also referred to as “systemic therapy”.
  • Types of Systemic Cancer Therapies: Includes endocrine therapy, molecularly targeted therapy, and immunotherapy.
  • Common Misconception: Chemotherapy is often viewed as the standard cancer drug treatment, but other forms exist that may not be classified as chemotherapy.

Types of Cancer Therapy

  • Local Therapies: Treat cancer in a specific area.

    • Examples:
    • Surgery: Surgical removal of tumors
    • External Beam Radiation Therapy: Primarily local targeting.

  • Systemic Therapies: Address cancer throughout the body.

    • Examples:
    • Drug therapies
    • Cellular therapies
    • Radiation administered like drugs (oral or IV).

Chemotherapy Drug Classes

  • Mechanisms of Action: Target and damage proliferating cells, impacting DNA or the mitotic apparatus.
  • Chemotherapy Categories:
    • Alkylating Agents:
    • Transfer alkyl groups to DNA and damage it in all cell cycle phases.
    • Antimetabolites:
    • Interfere with DNA synthesis; can mimic purines/pyrimidines.
    • Topoisomerase Inhibitors:
    • Prevent DNA unwinding and replication.
    • Antimicrotubule Drugs:
    • Disrupt microtubule function during cell division.

Detailed Mechanisms of Chemotherapy Drugs

Alkylating Agents

  • Mechanism: Alkyl groups react with DNA, causing cross-linking and damage.
  • Types: Bifunctional agents have two reactive groups for more effective DNA damage.

Platinum-based Chemotherapy

  • Prototype: Cisplatin, discovered through electric current experiments with platinum.
  • Mechanism of Action: Similar to alkylating agents; forms DNA cross-links.

Antimetabolites

  • RNA/DNA Interaction:
    • 5-FU (Fluorouracil):
      • Active metabolites inhibit enzymes crucial for nucleotide synthesis (thymidylate synthase).
  • Cytosine Arabinoside (Ara-C):
    • Inhibits DNA polymerase leading to halted DNA synthesis.
  • Gemcitabine:
    • Inhibits ribonucleotide reductase affecting nucleic acid production.

Topoisomerase Inhibitors

  • Classes: Camptothecins (Topo I), Epipodophyllotoxins, Anthracyclines (Topo II).
    • Stabilizes enzyme-DNA complexes causing double-stranded breaks leading to cell death.

Antimicrotubule Agents

  • Mechanism: Bind to tubulin and disrupt microtubule dynamics essential for mitosis.
  • Types: Vinca alkaloids (Vincristine, Vinblastine) and taxanes (Paclitaxel).

Resistance Mechanisms

  • Cancer Cell Resistance:
    • Tumor microenvironment impeding drug efficacy.
    • Alterations in drug influx/efflux impacts uptake.
    • Enhanced DNA repair mechanisms lead to insensitivity.

Clinical Considerations

  • Toxicities:
    • Affect rapidly dividing healthy cells: hair loss, gastrointestinal issues, bone marrow suppression.
  • Neurological Effects: Nerve damage leading to neurological toxicities and nausea/vomiting due to chemoreceptor activity in the brain.
  • Cancer Mitigation: Chemotherapy can lead to secondary cancers and other organ-specific damages over time.

Chemotherapy Efficacy

  • Applications:
    • Curative in disseminated cancers.
    • Adjuvant treatment post-surgery and control of micrometastases.
    • Combination with other therapies (e.g. radiation) can enhance efficacy.
    • Palliative care for advanced cancers.

Conclusion

  • Emphasis: While chemotherapy remains critical in cancer treatment, new paradigms like targeted therapy and immunotherapy are emerging as alternatives that continue to advance cancer care excellence.