Cancer Therapy Lecture 6: Targeted Therapy

Targeted Therapy in Cancer

• Targeted therapy is a type of cancer treatment that controls how cancer cells grow, divide, and spread.
• It is the foundation of precision medicine.

Types of Targeted Therapy in Cancer

• Small-molecule drugs:
  • Have a low molecular weight that can easily enter cancer cells.
  • Specifically target substances within the cell, blocking their function.
  • Have advantages like high potency and low toxicity due to their ability to spare normal cells.
• Monoclonal antibodies (MABs):
  • Engineered proteins produced in the lab to attach to specific targets found on cancer cells.
  • Can mark cancer cells, making them more visible to the immune system for destruction.

Key Characteristics of Monoclonal Antibodies

• Exquisite Specificity: MABs precisely recognize cancer-related proteins.
• Long Serum Half-Life: They persist in the bloodstream, allowing sustained therapeutic effects.
• High Affinity: MABs bind tightly to their targets.
• Immune Effector Functions: They can engage immune responses against cancer cells.

Strategies of Targeted Therapy Against Cancer

• Help the immune system destroy cancer cells.
• Stop cancer cells from growing by interrupting signals that cause them to grow and divide without order.
• Stop signals that block blood vessel formation.
• Deliver cell-killing substances to cancer cells.
• Starve cancer of hormones needed for growth.

Monoclonal Antibodies

• Can be combined with toxins, chemotherapy drugs, or radiation.
• Enhance specificity by targeting cancer-specific markers.
• Examples include trastuzumab (Herceptin) for HER2-positive breast cancer and rituximab for B-cell lymphomas.

Cancer Vaccines

• Definition: Cancer vaccines are a form of immunotherapy designed to educate the immune system about what cancer cells “look like”.
• Objective: They help the immune system recognize and eliminate cancer cells.
• Unlike preventive vaccines, cancer treatment vaccines focus on existing cancer cells.
• Types of Cancer Vaccines:
  • Therapeutic Cancer Vaccines: Elicit de novo T cell responses targeting tumor antigens.
  • Antigen Selection and Delivery Systems: Researchers have pioneered cancer vaccine design by selecting appropriate antigens and developing effective antigen-delivery systems.

Cytokines

• Soluble proteins that mediate cell communication within the tumor microenvironment (TME).
• Interleukins (ILs) and interferons (IFNs) are examples of cytokines that have been extensively studied.
• Challenges:
  • High toxicity due to systemic effects.
  • Low efficacy, especially in advanced-stage cancers.
  • Short half-life and biodistribution.

Immunotherapy Administration

• Different forms of immunotherapy may be given in different ways:
  • Intravenous (IV).
  • Oral.
  • Topical.
  • Intravesical.

Advantages and Challenges of Immunotherapy

• Advantages:
  • Precision: Targets cancer cells while sparing normal tissues.
  • Reduced Toxicity: Fewer side effects compared to traditional chemotherapy.
  • Personalization: Tailored to individual patients based on tumor characteristics.
• Challenges and Future Directions:
  • Clinical Response Rate: Continual efforts are needed to improve overall response rates.
  • Biomarkers: Identifying biomarkers can guide treatment selection.
  • Combination Approaches: Combining immunotherapy with other modalities may enhance efficacy.