Personalized Medicine In The Treatment of Cancer

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