L18 cancer treatment

2018 Nobel Prize in Physiology/Medicine

  • Awardees: James P. Allison and Tasuku Honjo

  • Discovery: Cancer therapy by stimulating the immune system to attack tumor cells.

  • Key Concepts:

    • Cancer: A group of diseases characterized by uncontrolled cell growth that can evade the immune system.

    • T Cells: A type of white blood cell that includes proteins acting as 'brakes' for immune response, which can be targeted for cancer treatment.

CTLA-4

  • Function: Acts as a brake for the immune response.

  • Research: James Allison developed an antibody to bind to CTLA-4, inhibiting its function, facilitating an immune attack on cancer.

  • Results: Successful in mice and later in human trials.

PD-1 Protein

  • Function: Another immune brake discovered by Tasuku Honjo.

  • Mechanism: Its blockage allows immune response and has shown effectiveness against various cancers, including metastatic ones considered untreatable.

Significance of Research

  • Established a new approach to cancer treatment, leading to several clinical trials with positive results observed in patients across multiple cancer types.

Understanding Cancer

  • Growth Control: Cancer represents a loss of normal growth control involving multiple mutations and failures in cell suicide mechanisms.

The Role of BRCA1

  • Function: Helps repair damaged DNA and prevent mutations.

  • Association with Cancer: BRCA1 mutations increase cancer risk as they impair DNA repair mechanisms.

Chromosomal Differences in Cancer

  • Normal Cells: Display organized chromosomal structures.

  • BRCA1 Mutant Cancer Cells: Exhibit numerous mutations and genomic rearrangements.

Challenges in Treating Cancer

  • Specificity: Cancer cells closely resemble normal cells, making targeted therapies difficult.

  • Personalization: Variability between individual cancers complicates treatment plans.

Current Treatment Strategies

Traditional Methods

  • Surgery: Oldest approach aiming to physically remove tumors; effectiveness can vary.

  • Chemotherapy: Targets rapidly dividing cells, although it affects normal cells too.

    • Example: Taxol interferes with the mitotic spindle.

    • History: First discovered during World War I as chemicals affecting white blood cells.

New Strategies

  • Personalized Medicine: Focuses on analyzing tumor mutations to tailor treatments.

  • Combination Therapies: Designed to address the challenge of drug resistance.

Cancer Immunotherapy

  • Utilizes the immune system to combat cancer effectively.

Types of Immunotherapy

  • Antibody Therapy: E.g., Herceptin targets HER2-positive tumors.

  • CAR T-cells: Engineering patient’s immune cells for targeted cancer cell destruction.

Case Studies

  • Barbara Bradfield: Experienced cancer recurrence but achieved long-term remission through clinical trial participation highlighting the efficacy of HER2 antibody therapy.

Mechanism of Action

  • Cytotoxic T Cells: Identify and kill cancerous cells by recognizing abnormal signals.

    • CAR T-cell Therapy: Involves engineering T-cells to target specific cancer markers with an emphasis on effective, albeit risky outcomes.

Side Effects in Immunotherapy

  • Risks associated with treatments, including loss of normal cells and severe immune responses (Cytokine Storms).

Advanced Therapies

  • Immune Checkpoint Inhibitors: Target checkpoints like PD-1, which cancer cells exploit to evade immune detection.

  • New FDA-approved drugs like Keytruda facilitate immune response against tumors.

Emerging Technologies

  • Cancer Vaccines: Personalized based on individual tumor mutations, under clinical trials similar in technology to COVID-19 vaccines.