Pharmacology 2 - Cancer Therapies

Pharmacology 2 - Cancer Therapies

• General Problems with Anti-Cancer Therapies:
  • Lack of selectivity: Difficult to target cancer cells without harming normal cells.
  • Off-target side effects: Treatments can harm healthy tissues.
  • Drug resistance: Cancer cells can develop mechanisms to expel drugs.
  • Patient-specific factors: Traditional treatments don't always account for individual genetic variations.
  • Cancer diagnosis challenges: Symptoms can be non-specific, leading to late diagnoses; few good biomarkers to detect cancer earlier.

Approaches to Cancer Treatment

• Surgery: Invasive procedure to remove tumors. Can also be used for prevention and debulking (removing bulk before chemotherapy).
• Radiotherapy:
  • External beam: High-energy radiation directed from outside the body, widely used.
  • Internal brachytherapy: Radioactive "seeds" placed inside the body.
  • Both techniques cause DNA damage, affecting both cancer and normal cells.
• Chemotherapy:
  • Interferes with cell cycle, aiming to inhibit cell division and replication.
  • Many agents target S phase (DNA replication) or M phase (mitosis).
• Targeted Therapies:
  • More specific than traditional approaches; they target certain pathways crucial to cancer cell growth or survival.
  • This is done, for example, through: inhibiting growth and death, hormones, and cell signalling.

Issues with Chemotherapy

• Cell Targeting: Cytotoxic drugs target rapidly dividing cells.
• Common Toxicities:
  • Myelosuppression (reduced bone marrow function, leading to infections, anemia, and low platelets).
  • Increased risk of infection.
  • Nausea and vomiting.
  • Diarrhea and mucositis.
  • Hair loss (alopecia).
  • Other toxicities include nephrotoxicity, neurotoxicity, cardiovascular toxicity.

Approaches to Treating Cancer: Targeted Therapy – Interfering with Specific Pathways

• Targeting Growth & Death Pathways:
  • Apoptosis pathways (e.g., Bcl-2)
  • Oncogenes and tumor suppressors (e.g., Ras, Src, p53)
  • Cell growth/proliferation pathways (e.g., Akt, PI3K)
• Targeting Hormones:
  • Blocking estrogen signalling (e.g., tamoxifen)
  • Blocking androgen signalling
• Targeting Cell Signalling:
  • Tyrosine kinase inhibitors (e.g., for HER2/neu, EGF, VEGF).
  • Angiogenesis inhibitors (e.g., bevacizumab)

Targeting Growth Signaling: VEGF

• VEGF (Vascular Endothelial Growth Factor): A protein crucial for blood vessel growth
• Cancer cells can overexpress VEGF protein to grow new blood vessels supplying tumor cells.

Summary

• **General Issues:**Current anti-cancer strategies have challenges like lack of specificity and off-target effects, and the pace of advancement remains slow.
• Historical Trends: Success in cancer diagnosis/treatment is somewhat "illusionary" as modern diagnostics detect tumors earlier.
• Different Treatment Approaches: Surgical approach as the most "cure-focused" for prevention. Radiotherapy and chemotherapy directly target rapidly dividing cells, while targeted therapies are designed to affect cancerous cells with a lower impact on healthy cells.

This quiz explores the challenges and approaches to cancer therapies covered in Pharmacology 2. Key topics include the lack of selectivity in treatments, side effects, and various treatment methods such as surgery and radiotherapy. Test your understanding of these critical concepts in cancer treatment.