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.