cancer care engineering: the cancer prevention perspective dorothy teegarden, ph.d. oncological...
TRANSCRIPT
Cancer Care Engineering:
The Cancer Prevention Perspective
Dorothy Teegarden, Ph.D.
Oncological Sciences Center
Lead, Cancer Prevention
and Control Program
Department of Foods and Nutrition
Cancer Prevention Impact• Diet
–30% of cancer deaths are related to diet (Doll, 1981).
• Tobacco use
–30% or 170,000 cancer deaths in the United States in 2006 (ACS, 2006).
• Other modifiable factors
–Environmental exposures
–Obesity
–Lack of physical activity.
• Could achieve by 2015 (IoM, 2004):
–19% decline in new cancer cases
–29% decline in the rate of cancer deaths
Multistage Cancer ProgressionInitiation
EnvironmentalGenetic
NormalGrowth
Preneoplasm
PromotionEnvironmental
Genetic
NeoplasmBenign
Or Malignant
Identify and/orPrevent Exposures
Very Early DetectionIdentify Genetic Risks
Cancer Prevention/Chemoprevention
Risk/Benefit
Normal Initiation Promotion Progression Metastases
Multi-stage Carcinogenesis
Cancer Prevention/Chemoprevention
Epidemiology
Biomarkers/ImagingEarly Detection
MolecularMechanisms
Clinical Trials Policy
BehavioralModeling
HealthcareSystems/Communication
Modifiable/Environment
BehaviorModificationMethodology
Animal Models
ChemopreventiveCompounds
Genetics
Cells
Nutrition
Cancer Research in Indiana
• Purdue University• NCI Cancer Center• Oncological Sciences
Center
• Indiana University • NCI Cancer Center• IU School of Medicine
• Hoosier Oncology Group
• Family Practice Network
Oncological Sciences CenterResearch Areas
• Cancer Prevention and Control
• Cancer Nanotechnology
• Cancer Biomarkers
• Novel Engineered Diagnostic and Therapeutic Devices
• Cancer Care Engineering
A Systems Approach to the Prevention & Treatment of Cancer
Cancer Care Engineering
Cancer Care Engineering Goals
We want to know who will develop specific cancers
(environment/gene interactions) and what strategies will prevent the development of that cancer.
Cancer Prevention and Chemoprevention
Cancer Prevention & Chemoprevention
• Cancer Prevention by Dietary Agents
–Nutrient and botanical
• Chemoprevention
• Very early detection
–Biomarkers and imaging
• Identification of risk factors
• Behavioral modification/Public Policy approaches to reduce risk
–Smoking cessation
–Reducing incidence of obesity
• Application of knowledge in healthcare settings
Treat Cancer and Cancer Prevention as a System
• Interdisciplinary Team Approach
• Enabling Systems Infrastructure
• Data Integration
• Patient Data, Literature Data, HSR Data
• Rapid Communication
• Efficient clinical validation
• Hypothesis generation
• Community-based Approach
CCE ModelBedside to Bench and Back
1. Sample Acquisition/ManagementCommunity-based oncology clinics
Undiagnosed populations
2. Data AcquisitionOMICS, Prevention Data
Indiana University School of MedicineRegenstrief InstitutePurdue University
3. Data Storage/Query CenterPurdue University
4. Predictive Statistical ModelingPurdue University
5. Real-time Visualization of DataPurdue University
6. Immediate Clinical Analysis & Clinical FeedbackIndiana University Cancer Center
7. Discovery Research Driven by Model Predictions
Purdue UniversityIndiana University Cancer Center
New Directed SamplingIterative Models Refined
Predictive Outcomes Analyzed
CCE Leadership TeamPurdue University
• Don Bergstrom, PhD
• Richard Borch, MD, PhD
• Marietta Harrison, PhD
• Julie Nagel, PhD
• Joseph Pekny, PhD
• Dorothy Teegarden, PhD
IU Cancer Center
• Mark Kelley, PhD
• James Klaunig, PhD
• Pat Loehrer, MD
• Chris Sweeney, MBBS
• Stephen Williams, MD
Oncological Sciences Centere-Enterprise Center Regenstrief Center for Healthcare EngineeringPurdue Cancer Center
Immediate Communication A System Wide Awareness
• Instantaneous Picture of Indiana Cancer Care System
• Multidisciplinary Staffing
• Community Oncologist Accessibility
• Dissemination of New Data Patterns
• Allow Data Driven Resource Allocation
Study Design
Genetic Variants (SNPs) Oxidative Stress (enzymatic production
and removal) Epigenetic Methylation Vitamin D Metabolism Colon Cancer
Development and Progression
Colon Cancer Susceptibility: Role of Oxidative Stress (and Vitamin D)
Oxidative Stress ParametersVitamin D StatusDietary Intake
Environment
Bioinformatics
System Analysis Model 3. Input Clinical Data
(Disease Development in Healthy Controls, biomarkers)
4. Model Identifies Necessary New Data
5. Input Necessary New Data
2. Predict Subject Response to Intervention
6. Predict Development of Disease in Healthy Individuals and Effectiveness of Nutritional Interventions
Cancer Care EngineeringPrevention and Control
Situation Room
1. Input Patient “omics” Data Input Healthy Control “omics” Data
Biomarker Identification & Validation
Early Detection and Risk Assessment
www3.cancer.gov/atlasplus/
High Epithelial Cell Cancer Rates are Associated with Low UV Exposure
- 28 oN
- 35 oN
- 42 oN
500*
450
400
350
300
* Mean daily solar radiation in g-cal/cm2
Colon Cancer Susceptibility: Role of Oxidative Stress (and Vitamin D)
James Klaunig Center for the Environment; IU Cancer Center
Dorothy Teegarden Purdue University Cancer Center, Oncological Sciences Center
Mark Kelley IU Cancer CenterLisa Kamendulis IU Cancer Center
Oxidative Stress, Vitamin D and Colon Cancer
• Oxidative stress
– Balance oxidant>antioxidants
– Damage (proteins, lipid and nucleic acids)
– Cancer
• Factors that Impact Oxidative Stress
– Overproduction of reactive oxygen species
– Faulty or inadequate enzymatic antioxidant defenses
– Inadequate intake of antioxidants
– Faulty or inadequate DNA repair
– Association with genetic variants
• Vitamin D Status
– Colon cancer prevention
– Inhibits proliferation, induces differentiation, stimulates apoptosis
– Genetic variants associated with colon cancer progression
– Promote enhanced oxidative defenses
Colon Cancer Susceptibility: Role of Oxidative Stress (and Vitamin D)
Chemoprevention strategies involving both antioxidant and vitamin D supplementation may be
useful for preventing colon carcinogenesis.Hypothesis
The formation and progression of preneoplastic colon lesions (or a subset thereof) is dependent on the induction
of oxidative stress and damage that is due in part, to genetic susceptibility factors and/or dietary and lifestyle
factors that influence oxidative stress status.
Study Design
Genetic Variants (SNPs) Oxidative Stress (enzymatic production
and removal) Epigenetic Methylation Vitamin D Metabolism Colon Cancer
Development and Progression
Colon Cancer Susceptibility: Role of Oxidative Stress (and Vitamin D)
Oxidative Stress ParametersVitamin D StatusDietary Intake
Environment
Bioinformatics
Factors Influencing Serum 25OH D Levels
• White vs African American = +12.8 nmol/L• South vs North = +6.4 nmol/L• Low vs High BMI = +8.6 nmol/L• Active vs Inactive = +13.5 nmol/L• High vs Low Diet vitamin D = +10.4 nmol/L• Autumn vs Winter = +13.5 nmol/L
Giovannucci et al. J Natl Cancer Inst 2006;98:451
Active, skinny, white Southerner = +41.3 nmol/L!!!!
Systems Infrastructure
• Sample Acquisition
• OMIC Analyses
• Iterative Predictive Modeling
• Instant Feedback to Clinics
• Clinical Data Driving Basic Research
BEDSIDE
LABORATORY
Enabling Individualized Treatment & Prevention Plans
Project Long Term Goals• Establish Cancer Care System Infrastructure
• Provide Instantaneous Communication Vehicle
• Stratify Patients • Prevention Strategies
• Response to Therapy
• Clinical Trials
• ID and Validate Clinically Relevant Biomarkers
• ID Therapeutic Targets
• ID Barriers to Effective Healthcare Delivery