Slide 1

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


Slide 2

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


Slide 3

Multistage Cancer Progression
Initiation
Environmental
Genetic

Normal
Growth

Preneoplasm

Neoplasm
Promotion
Environmental
Genetic

Identify and/or
Prevent Exposures

Identify Genetic Risks

Very Early Detection

Benign
Or
Malignant


Slide 4

Cancer
Prevention/Chemoprevention
Multi-stage Carcinogenesis
Normal

Initiation

Promotion

Risk/Benefit

Progression

Metastases


Slide 5

Cancer Prevention/Chemoprevention
Genetics

Modifiable/Environment

Chemopreventive
Compounds

Behavioral
Modeling

Animal Models
Epidemiology

Molecular
Mechanisms

Clinical
Trials

Behavior
Modification
Methodology
Policy

Healthcare
Systems/Communication

Cells
Nutrition
Biomarkers/Imaging
Early Detection


Slide 6

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


Slide 7

Oncological Sciences Center
Research Areas

• Cancer Prevention and Control
• Cancer Nanotechnology
• Cancer Biomarkers
• Novel Engineered Diagnostic and

•

Therapeutic Devices
Cancer Care Engineering


Slide 8

Cancer Care Engineering
A Systems Approach to the
Prevention & Treatment of Cancer


Slide 9

Cancer Care Engineering Goals
Cancer Prevention and Chemoprevention
We want to know who will
develop specific cancers
(environment/gene interactions)
and what strategies will prevent
the development of that cancer.


Slide 10

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


Slide 11

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


Slide 12

CCE Model
Bedside to Bench and Back
1. Sample Acquisition/Management
Community-based oncology clinics
Undiagnosed populations

5. Real-time Visualization of Data
Purdue University

2. Data Acquisition
OMICS, Prevention Data
Indiana University School of Medicine
Regenstrief Institute
Purdue University

6. Immediate Clinical Analysis &
Clinical Feedback
Indiana University Cancer Center

3. Data Storage/Query Center
Purdue University

7. Discovery Research Driven by
Model Predictions
Purdue University
Indiana University Cancer Center

4. Predictive Statistical Modeling
Purdue University

New Directed Sampling
Iterative Models Refined
Predictive Outcomes Analyzed


Slide 13

CCE Leadership Team
Purdue University
IU Cancer Center
• Don Bergstrom, PhD
Mark Kelley, PhD
• Richard Borch, MD, PhD • James Klaunig, PhD
• Marietta Harrison, PhD • Pat Loehrer, MD
• Julie Nagel, PhD
• Chris Sweeney, MBBS
• Joseph Pekny, PhD
• Stephen Williams, MD
• Dorothy Teegarden, PhD

•

Oncological Sciences Center
e-Enterprise Center
Regenstrief Center for
Healthcare Engineering
Purdue Cancer Center


Slide 14

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


Slide 15

Colon Cancer Susceptibility: Role of
Oxidative Stress (and Vitamin D)
Study Design
Genetic Variants (SNPs)
Oxidative Stress (enzymatic production
and removal)
Epigenetic Methylation
Vitamin D Metabolism
Environment
Oxidative Stress Parameters
Vitamin D Status
Dietary Intake
Bioinformatics

Colon Cancer
Development
and Progression


Slide 16


Slide 17

Cancer Care Engineering
Prevention
and
Control
1. Input Patient “omics” Data
2. Predict Subject Response to Intervention
Input Healthy Control “omics”
Data

System Analysis
Model
6. Predict Development
of Disease in Healthy
Individuals and
Effectiveness of
Nutritional Interventions

Situation
Room

3. Input Clinical Data
(Disease
Development in
Healthy Controls,
biomarkers)

4. Model Identifies
Necessary New Data

5. Input Necessary
New Data
Biomarker Identification
& Validation

Early Detection and
Risk Assessment


Slide 18

High Epithelial Cell Cancer Rates are
Associated with Low UV Exposure

- 42 oN

- 35 oN

- 28 oN

* Mean daily solar radiation in g-cal/cm2
www3.cancer.gov/atlasplus/


Slide 19

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
IU Cancer Center
IU Cancer Center

Mark Kelley
Lisa Kamendulis


Slide 20

Oxidative Stress, Vitamin D
and Colon Cancer
•

•

Oxidative stress
• Vitamin D Status
– Balance oxidant>antioxidants
– Colon cancer prevention
– Damage (proteins, lipid and
– Inhibits proliferation, induces
nucleic acids)
differentiation, stimulates
– Cancer
apoptosis
Factors that Impact Oxidative Stress
variants associated
– Overproduction of reactive oxygen – Genetic
with colon cancer
species
progression
– Faulty or inadequate enzymatic
antioxidant defenses
– Promote enhanced oxidative
defenses
– Inadequate intake of antioxidants
– Faulty or inadequate DNA repair
– Association with genetic variants


Slide 21

Colon Cancer Susceptibility: Role of
Oxidative Stress (and Vitamin D)
Chemoprevention strategies involving both
antioxidant and vitamin D supplementation may be
Hypothesis
useful for preventing colon carcinogenesis.
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.


Slide 22

Colon Cancer Susceptibility: Role of
Oxidative Stress (and Vitamin D)
Study Design
Genetic Variants (SNPs)
Oxidative Stress (enzymatic production
and removal)
Epigenetic Methylation
Vitamin D Metabolism
Environment
Oxidative Stress Parameters
Vitamin D Status
Dietary Intake
Bioinformatics

Colon Cancer
Development
and Progression


Slide 23

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
Active, skinny, white Southerner = +41.3 nmol/L!!!!
Giovannucci et al. J Natl Cancer Inst 2006;98:451


Slide 24

Systems Infrastructure

• Sample Acquisition
• OMIC Analyses
• Iterative Predictive Modeling
• Instant Feedback to Clinics
• Clinical Data Driving Basic

BEDSIDE

LABORATORY

Research
Enabling Individualized
Treatment & Prevention Plans


Slide 25

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