Personalised Medicine notes

Personalised Medicine Overview

• Instructor: Dr. Elvira Mambetisaeva

• Contact: e.mambetisaeva@ucl.ac.uk

• Institution: UCL Division of Biosciences

Lecture Outline

• Overview of Personalised Medicine

  • Stratified Medicine

  • Introduction to Pharmacogenomics

  • Pharmacokinetics & Pharmacodynamics

  • Biomarkers

  • Apps, Devices, and Wearables

  • Future of Personalised Medicine

Evolution of Medicine

Past (1000 Years)

• Practices based on visible symptoms and intuitive diagnosis.

• Emphasis on anatomical knowledge.

Today (Last 10-100 Years)

• Shift towards biochemistry and cellular processes for diagnosis.

• Integration of genetics, molecular biology, and molecular imaging.

Future

• Individualized management through computer predictions for optimal therapies.

Definition of Personalised Medicine

• Tailors treatment to individual characteristics (genetics, lifestyle, environment).

• Aims for more effective treatments with fewer side effects, improving overall patient outcomes.

Precision Medicine

• Synonymous with Personalised Medicine.

• Variations exist in definitions among researchers.

Key Initiatives

• 2015 Precision Medicine Initiative launched by President Obama:

  • Focus on tailoring treatments similar to blood type matching in transfusions.

  • Vision of matching cancer treatments to genetic codes.

Concepts in Personalised Medicine

One-size-fits-all vs Personalization

• Traditional medicine: uniform therapies for all.

• Stratified medicine: groups based on specific disease mechanisms or responses.

• Personalized approaches consider:

  • Patient preferences

  • Clinical features

  • Medication history

  • Environmental factors

  • Behavior and habits

Stratified Medicine

• Divides patients into distinct groups based on molecular biomarkers and treatment responses.

• Utilizes diagnostic tests for group classification.

Key Principles of Personalised Medicine

• Genetic Basis: Influences drug metabolism and treatment responses.

• Environmental Factors: Lifestyle and exposure to harmful elements are significant.

Patient Stratification

• Involves categorizing diverse patient cohorts by:

  • Age

  • Clinical presentation

  • Medical history and imaging results

• Uses genomic sequencing, biomarkers, and metabolite analysis.

Breast Cancer Heterogeneity

• Breast Cancer: Most common cancer type, highly heterogeneous.

• Differences include:

  • Clinical presentation variations

  • Molecular and tissue morphologies

  • Varying responses to treatments and recurrence rates.

Treatment Personalization in Breast Cancer

• Hormone receptor testing (ER/PR/HER2): Crucial for treatment decision-making.

  • ER+ Tumors: Up to 75% of breast cancers, often responsive to anti-estrogen treatments.

  • HER2+ Tumors: Associated with rapid growth; responsive to Trastuzumab.

  • Triple-negative cancers: Lack hormone receptors; present challenges in treatment.

Advantages of Personalised Medicine

1. Early Detection: Tailored approaches improve accuracy.

2. Treatment Efficacy: Improved outcomes through targeted therapies.

Challenges in Breast Cancer Treatment

• Tumor heterogeneity complicates treatment options.

• Presence of resistance mechanisms and disparities in access to effective diagnostics and treatments.

Introduction to Pharmacogenetics

• Examines genetic variations affecting drug efficacy and reactions.

• Pharmacogenomics: Focuses on the overall genome's role in drug response.

Drug Response Variations

• Genetic and environmental factors affect individual drug responses.

• Adverse Drug Reactions (ADRs): Significant morbidity causes in developed countries.

Factors Influencing Drug Interactions

• Genetic variations account for 20-25% of variability in drug response.

• Other influencing factors include:

  • Environmental exposures

  • Physiological states (age, sex, disease state)

Adverse Drug Reactions Statistics

• ADRs: Leads to 250,000 admissions per year in the UK.

• Associated costs estimated at £466 million annually.

Historical Context of Pharmacogenetics

• Highlights crucial milestones and discoveries from the early 1900s to the Human Genome Project.

Drug Metabolism Basics

• Pharmacokinetics (PK): Involves drug absorption, distribution, metabolism, and excretion.

• Pharmacodynamics (PD): Studies drug effects on the body.

Cytochrome P450 Enzymes

• Critical in drug metabolism; over 50 CYP450 enzymes identified.

• Key classifiers include CYP3A4 and CYP2D6, which metabolize substantial drug proportions.

Genetics & Drug Response

• Genetic polymorphisms affect drug metabolism; different populations show distinct variations in metabolic responses.

Clinical Application of Pharmacogenetic Testing

• First genotype test: Established for guiding medication selection based on CYP450 polymorphisms.

• Economic considerations obstruct widespread adoption.

Personalized HIV Treatment

• Tailoring treatments based on genetic profiles enhances the quality of care for HIV patients.

• Monitoring drug metabolism through CYP450 enzymes critical for effective antiretroviral therapy.

Genetic Testing Challenges

• Issues include establishing clinical validity, standardization, and evidence-based practices.

Ethics in Genetic Testing

• Ethical concerns surrounding privacy, costs, access, equity, and representation in genetic studies.

Conclusion on P4 Medicine

• Emphasizes predictive, personalized, preventive, and participatory healthcare approaches leveraging omics technologies.

Biomarker Discovery in Personalised Medicine

• Biomarkers: Biological indicators of disease or therapeutic responses.

• Importance of clinical relevance and rigorous study designs for acceptance into practice.

Apps and Wearable Technology

• Applications designed for chronic condition management and patient engagement in healthcare.

• Features should include reliability, ease of use, and accessibility.

Future Directions

• Emphasis on interdisciplinary collaboration for advancing personalized healthcare technologies.