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Pharmacogenomics. Jatinder Lamba Associate Professor Experimental and Clinical Pharmacology College of Pharmacy. Moderate or poor response. “One size doesn’t fit all” : Inter-individual variability in response. Good Response No adverse effects. All Patients with Same Diagnosis.
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Pharmacogenomics Jatinder LambaAssociate Professor Experimental and Clinical Pharmacology College of Pharmacy
Moderate or poor response “One size doesn’t fit all” : Inter-individual variability in response Good Response No adverse effects All Patients with Same Diagnosis Increased toxicity risk
No drug is safe and effective in a same way for everyone Spear et al, 2001
Variation is the spice of life • Human genome has 3.2 billion base pairs • Any two genomes are 99.9 % identical • 0.1% => every two genomes have 3.2 million differences IHGSC. Nature (2001) 409 860-921
Pharmacogenetics/genomics How inherited genetic differences influence treatment response to drugs Pharmacology + Genetics Key is to understand to what degree genetics is valuable to a given disease/therapy AND use this information to • Avoid adverse drug reactions • Maximize therapeutic efficacy • Preselect responsive/nonresponsive patients and tailor therapy accordingly
Ongoing Pharmacogenomic Projects (Lamba Lab) • Pharmacogenomics and PharmacoEpigenomics of nucleoside analogs in AML patients (NIH funded). • PGx of antibody targeted therapy in pediatric AML (NIH funded). • PGx of platinating agents and taxanes in ovarian and lung cancer patients. • PGx of cyclophosphamide in BMT patients.
There is little difference between human and veterinary species in regard to the magnitude of inter-subject variability in drug pharmacokinetics and pharmacodynamics. • Despite the lack of genetic information in veterinary medicine, breed specific differences in response to endogenous and exogenous substances have been reported across a range of species, including cattle (1), sheep (2), chickens (3), pigs (4), and dogs.