Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

4 Applying
Pharmacogenomics
in Drug Discovery
and Development
Ruth Vinall
CONTENTS
Key Concepts............................................................................................................ 75
Introduction............................................................................................................... 76
Use of Pharmacogenomics to Identify Drug Targets................................................ 76
Target Validation.......................................................................................................79
Assessing “Druggability” of a Target and Lead Drug Discovery Strategies............80
Pharmacogenomics Considerations during Preclinical Studies
of Potential Lead Drugs............................................................................................82
Pharmacogenomics and Clinical Studies..................................................................84
Conclusions...............................................................................................................89
Study Questions........................................................................................................89
References.................................................................................................................90
KEY CONCEPTS
• Identification of genetic alterations that are causative in the disease process
allows for the development of targeted therapies that are likely to have
higher efficacy and lower toxicity compared to nontargeted therapies.
• Polymorphisms that alter binding of the drug to a target, and drug absorption;
distribution; metabolism; and excretion, as well as transport, can affect
both drug efficacy and toxicity.
• In silico, cell line, animal model studies can be used to assess “druggability”
of targets and to predict clinical efficacy and toxicity in patients.
• Pharmacogenomic studies can be used to identify new indications for
existing drugs.
• Inclusion of patients from a diverse patient population in pharmacogenomic
analyses is important to maximize benefit and minimize toxicity for all patients.
• Pharmacogenomic analysis of biospecimens from patients recruited in
phase I, II, and III clinical trials can help guide subsequent patient selection
and drug usage.
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