Personalized Medicine In The Treatment of Cancer
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Transcript of Personalized Medicine In The Treatment of Cancer
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Personalized Medicine In The Treatment of Cancer
Elvin T. Price, Pharm.D.,Ph.D.Assistant Professor Pharmaceutical Sciences University of Arkansas for Medical Sciences
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Objectives
• Provide an introduction to the principles of pharmacogenetics/genomics (PGx) and personalized medicine (PM)
• Describe the clinical relevance of PGx/PM to the management of cancer
• Provide insight on the future of PGx/PM and cancer
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Time Magazine May 27, 2013
“Her preventive mastectomy raises important issues about genes, health and risk”
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Personalized Medicine Is Headed Your Way
• Direct to consumer genomics companies are becoming increasingly popular and the prices are becoming increasingly affordable.
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Personalized Medicine Is Headed Your Way
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Personalized Medicine Is Headed Your Way
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AMDPA and NMA MembersPersonalized Medicine Is Headed Your Way
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Introduction
• Clinical observations of inherited differences in drug effects were first documented in the 1950s, giving rise to the field of pharmacogenetics, and later pharmacogenomics.
• The early pharmacogenetic examples were those with distinct phenotypes that could be easily characterized, understanding of the molecular basis for the phenotypes came later.
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Genetic Variation
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Genetic Variability Influences Response to Pharmacotherapy
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Genetic Variability Influences Targets of Pharmacotherapy
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Genetic Variability Influences Drug Metabolism Enzymes
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Genetic Variability Influences Drug Metabolism: Transporters
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Moving Towards Pharmacogenomics
Ann Intern Med 2006;145:749.
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Pharmacogenomics
TARGETSMETABOLIZING
ENZYMESTRANSPORTERS
PHARMACOKINETICSPHARMACODYNAMICS
Variability in Efficacy/Toxicity
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The Goal of PGx and PM
Patients with same diagnosis
Predicted increasedtoxicity risk
Decrease dose or usedifferent drug
Predicted goodresponse totested drug
Predicted poor or nonresponse
Use different drug
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PGx Biomarkers Are Useful When Prescribing Tamoxifen
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Estrogen Receptor Status Influences Response To Tamoxifen
Estrogen Receptor Negative Estrogen Receptor Positive
Tumor Status
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CYP2D6 Genotypes Influence Response To Tamoxifen
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CYP2D6 and ABCC2 Genotypes Influence Response To Tamoxifen
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CYP2D6 and ABCC2 Genotypes Influence Response To Tamoxifen
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CYP2D6 and ABCC2 Genotypes Influence Response To Tamoxifen
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Mid CE Exam
Patients with same diagnosis
Predicted increasedtoxicity risk
Decrease dose or usedifferent drug
Predicted goodresponse totested drug
Predicted poor or nonresponse
Use different drug
• Based on the previous slides, predict a response to tamoxifen for the following patient:
• 55 y/o with Estrogen receptor negative tumors and is a CYP2D6 poor metabolizer.
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Breakthroughs In BCA PGx Hit The Popular Press and Scientific Literature Simultaneously
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Breakthroughs In BCA PGx Hit The Popular Press and Scientific Literature Simultaneously
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Breakthroughs In BCA PGx Hit The Popular Press and Scientific Literature Simultaneously
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Current Trends Summary
• The rapid advances in genomics technology is being embraced and maximized in the treatment of cancers
• These advances are also discovering molecular links to other disease states that are associated with cancer risks
• Many drugs used in the treatment of cancers are being released with companion genetic diagnostic tests
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Current/Future Directions:Big Data
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Gene Expression Patterns Link Previously Unrelated Diseases
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Breast Cancer Cell Expression Patterns Link to Other Diseases
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Future Directions in BCA PGx
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Future Directions in BCA PGx
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Current/Future Directions:Clues From Big Data
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Current/Future Directions:Clues From Big Data
The ACCORD Study. Simvastatin + Fenofibrate in Type 2 Diabetes
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Current/Future Directions:Clues From Big Data
Manuscript in prep. ET Price
Fenofibrate Effects on Nuclear Hormone Receptor Expression in Endothelial Cells
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Current/Future Directions:Clues From Big Data
Manuscript in prep. ET Price
Fenofibrate Effects on Nuclear Hormone Receptor Expression in Endothelial Cells
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Networked Analyses of Genetic Variants Will Identify Additional Cancer Risk Genes:
ABCRP Pilot Proposal
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Current Directions in PGx-PM
Patients with same diagnosis
Predicted increasedtoxicity risk
Decrease dose or usedifferent drug
Predicted goodresponse totested drug
Predicted poor or nonresponse
Use different drug
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Current Pharma Strategies
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Current Pharma Strategies
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Current Pharma Strategies
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Current Pharma Strategies
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Current Pharma Strategies
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FDA Perspective On PM
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FDA Genomics Group of CDER
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Link To FDA PGX Information
• http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/default.htm
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Summary
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Q/A
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