PGx and Targeted Therapy Flashcards
Define Target Therapy
Treatments that target specific characteristics of diseased cells
- Usually less harmful
Target therapies can be
Various forms: small molecules, RNA/DNA-based oligonucleotides antibodies and peptides
Can things affect target therapy?
Yes PGx factors may affect efficacy and side effects of target therapy
Key factors in discovery and development of target therapy
New technology
New targets
Target validation in early development
PREDICTIVE MODELS
Disease can have different targets like:
Foreign pathogens
Host disease causing genes/proteins
Host internal and external environments
Targets may be at what levels
Molecular Cellular Tissue/Organ System Whole body Population
Effects of targeted therapy can be:
Physiological
Biochemical
Functional
Target discovery process
Find genes and related them to a disease (positive association)
Criteria
Causal relation Correlation with disease status Specificity Affinity Mode of action Regulation of effects
Methods of Target Validation
Molecular/Genetic Biochemical Physiological Pharmacological/Toxicological Population
Testing Systems
Cell-free Cell Organ Small animal Monkey Humans Bioinformatics
Evaluation
Qualitative
Quantitative: dose effect (individual), dose-response (group level)
Biological effects vs statistical significant
EGFR Drugs
Erlotinib (lung)
Cetuximab (colon)
Oncotype Dx
21 gene assay (16 cancer related)
Low, intermediate and high risk
MammaPrint
70 gene assay
Breast cancer
Aggressive therapy if poor prognosis
Risk of distant metastasis
PGx Factors in Target Therapy
Pathogens Targeted gene Gene associated metabolism and disposition of drug Signaling pathway Interactions Physiology/disease status
