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 Members
Personalized 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
TARGETS
TRANSPORTERS
PHARMACODYNAMICS
METABOLIZING
ENZYMES
PHARMACOKINETICS
Variability in
Efficacy/Toxicity
The Goal of PGx and PM
Patients with same diagnosis
Predicted good
response to
tested drug
Predicted poor or
nonresponse
Use different drug
Predicted increased
toxicity risk
Decrease dose or use
different drug
PGx Biomarkers Are Useful
When Prescribing Tamoxifen
Estrogen Receptor Status
Influences Response To Tamoxifen
Tumor Status
Estrogen Receptor Negative
Estrogen Receptor Positive
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
• 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.
Patients with same diagnosis
Predicted good
response to
tested drug
Predicted poor or
nonresponse
Use different drug
Predicted increased
toxicity risk
Decrease dose or use
different drug
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
Fenofibrate Effects on Nuclear Hormone Receptor Expression in Endothelial Cells
Manuscript in prep. ET Price
Current/Future Directions:
Clues From Big Data
Fenofibrate Effects on Nuclear Hormone Receptor Expression in Endothelial Cells
Manuscript in prep. ET Price
Networked Analyses of Genetic Variants Will
Identify Additional Cancer Risk Genes:
ABCRP Pilot Proposal
Current Directions in PGx-PM
Patients with same diagnosis
Predicted good
response to
tested drug
Predicted poor or
nonresponse
Use different drug
Predicted increased
toxicity risk
Decrease dose or 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/ScienceResearc
h/ResearchAreas/Pharmacogenetics/defa
ult.htm
Summary
Q/A