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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. Objectives. Provide an introduction to the principles of pharmacogenetics/genomics (PGx) and personalized medicine (PM) - PowerPoint PPT Presentation
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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
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
Time Magazine May 27, 2013
“Her preventive mastectomy raises important issues about genes, health and risk”
Personalized Medicine Is Headed Your Way
• Direct to consumer genomics companies are becoming increasingly popular and the prices are becoming increasingly affordable.
Personalized Medicine Is Headed Your Way
Personalized Medicine Is Headed Your Way
AMDPA and NMA MembersPersonalized Medicine Is Headed Your Way
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.
Genetic Variation
Genetic Variability Influences Response to Pharmacotherapy
Genetic Variability Influences Targets of Pharmacotherapy
Genetic Variability Influences Drug Metabolism Enzymes
Genetic Variability Influences Drug Metabolism: Transporters
Moving Towards Pharmacogenomics
Ann Intern Med 2006;145:749.
Pharmacogenomics
TARGETSMETABOLIZING
ENZYMESTRANSPORTERS
PHARMACOKINETICSPHARMACODYNAMICS
Variability in Efficacy/Toxicity
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
PGx Biomarkers Are Useful When Prescribing Tamoxifen
Estrogen Receptor Status Influences Response To Tamoxifen
Estrogen Receptor Negative Estrogen Receptor Positive
Tumor Status
CYP2D6 Genotypes Influence Response To Tamoxifen
CYP2D6 and ABCC2 Genotypes Influence Response To Tamoxifen
CYP2D6 and ABCC2 Genotypes Influence Response To Tamoxifen
CYP2D6 and ABCC2 Genotypes Influence Response To Tamoxifen
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.
Breakthroughs In BCA PGx Hit The Popular Press and Scientific Literature Simultaneously
Breakthroughs In BCA PGx Hit The Popular Press and Scientific Literature Simultaneously
Breakthroughs In BCA PGx Hit The Popular Press and Scientific Literature Simultaneously
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
Current/Future Directions:Big Data
Gene Expression Patterns Link Previously Unrelated Diseases
Breast Cancer Cell Expression Patterns Link to Other Diseases
Future Directions in BCA PGx
Future Directions in BCA PGx
Current/Future Directions:Clues From Big Data
Current/Future Directions:Clues From Big Data
The ACCORD Study. Simvastatin + Fenofibrate in Type 2 Diabetes
Current/Future Directions:Clues From Big Data
Manuscript in prep. ET Price
Fenofibrate Effects on Nuclear Hormone Receptor Expression in Endothelial Cells
Current/Future Directions:Clues From Big Data
Manuscript in prep. ET Price
Fenofibrate Effects on Nuclear Hormone Receptor Expression in Endothelial Cells
Networked Analyses of Genetic Variants Will Identify Additional Cancer Risk Genes:
ABCRP Pilot Proposal
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
Current Pharma Strategies
Current Pharma Strategies
Current Pharma Strategies
Current Pharma Strategies
Current Pharma Strategies
FDA Perspective On PM
FDA Genomics Group of CDER
Link To FDA PGX Information
• http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/default.htm
Summary
Q/A