1. Update on Cancer Research in Iowa
George Weiner, MD

2. Cancer Research Categories
Basic Cancer Research
Translational and Clinical Cancer Research
Clinical Cancer Research (T1)
Phase 0, I, II, III, IV Clinical Trials
Comparative Effectiveness (T2)
Prevention
Early Detection
Therapy
Quality of Life

3. Translational Research
T1 - The transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans
T2 - The translation of results from clinical studies into everyday clinical practice and health decision making

4. Translational Research
Basic
Research
Laboratory
Research
Clinical
Bench to
Bedside
Bedside to
Bench T1
New
Treatments

5. Translational Research
Clinical Research
Community to
Clinical
Use
Better
Treatments
Community to
Clinical Research T2
New
Treatments
Comparative
Effectiveness
Research

6. Cancer Research in Iowa
Non-Academic
Oncology Practices
T1 T2
Clinical
Basic

7. 190 Faculty Free Radical Biology Institute for Biomedical Imaging
Tumor
Imaging
Free
Radicals
Cancer
Biology
Signaling
and
Experimental
Therapeutics
Genomics
Cell
Growth
Immunology
Immunotherapy
Epidemiology
CTSA
College of
Public Health
SEER
190 Faculty
Immunology
Center for
Bioinformatics
Genetics

8. Examples across spectrum of collaborative cancer research taking place at the Holden Comprehensive Cancer Center
Sleeping beauty transposon and gene discovery
Aptamers to target cancer therapy
Psychological influences on cancer biology
TLR9 agonists from discovery to clinical evaluation
Enhancing Community-Based Cancer Control
Clinical Research

9. Sleeping Beauty mouse models of cancer
Conditional expression of Sleeping Beauty transposon in mice
Cancer gene discovery
Adam Dupuy
Todd Scheetz 9

10. Sleeping Beauty Transposon and Gene Discovery
Identify pathways and interacting genes in malignant transformation
Adam Dupuy
Todd Scheetz
Insertional Mutagenesis
Oncogene
Transposon
Acute Lymphoblastic Leukemia
Hepatocellular Cancer
Colorectal Cancer
Sarcoma Glioma
PNAS 2008, Cancer Res 2009a,
Cancer Res 2009b, Science 2009,
Nat Biotech 2009,
Tumor Suppressor
Tumor
Transposon

11. RNA aptamers in cancer therapy
Aptamer-siRNA to target PSMA (+) tumors (Nature Biotech, 2009)
Other surface targets – HER2, EGFR, 4-1BB
Other siRNA – NFkB, HPV E6/E7
Aptamer-based radiopharmaceuticals
Paloma Giangrande
Michael Schultz
James McNamara
Al Klingelhutz

12. TLR9 Agonists (CpG ODN) Discovery DevelopmentB
cell
Plasmacytoid
Dendritic
Cell NK T
Discovery
Proliferation of B Cells
Activation of Plasmacytoid Dendritic Cells
Activation of NK Cells
Bishop
Waldschmidt
Development
Malignant B-Cell
activation-induced cell death
Enhance response to antibody therapy
Immune adjuvant in cancer vaccination
Incorporation into nanoparticles for immunization
Lubaroff
Ballas
Salem
Weiner
Delivery (Clinical trials)
Single agent in lymphoma
Single agent in CLL
With rituximab in lymphoma
With radioimmunotherapy in lymphoma
Link

13. Biobehavioral Research
Psychological factors and cancer biology
Social isolation and tumor gene expression
Stress hormones and T cells / NK cells, angiogenesis and tumor cell invasion
Impact of complementary and alternative medicine on psychoneuro-immunologic pathways
Susan Lutgendorf
David Lubaroff
NCI R01 – Biobehavioral influences and
the ovarian tumor microenvironment
High Depression & Low Social Support
Low Depression & High Social Support
Doug Spitz
Lutgendorf et al. Host Factors and Cancer Progression: Biobehavioral Signaling Pathways and Interventions
JCO in press
Michael Goodheart

14. Enhancing Community-based Cancer Control
Incidence
CRC
Gerard Rushton
Iowa Research Network (IRENE) – a rural primary care practice-based research network
Late Stage
CRC
For many years Dr. Gerard Rushton, a program member who is an internationally known geographer, has been collaborating with the statewide cancer registry and the Iowa Cancer Consortium to develop maps that show variations in cancer incidence, late stage, and mortality across the state of Iowa using geographical information systems. Examples of these maps are presented for colorectal cancer incidence and late stage disease. The green circles indicate areas where these rates are low, whereas the red circles indicate areas where they are high. Such areas can be identified at various locations across the state. Iowa Cancer Consortium members have been using these maps to educate the residents and health care providers about the need for cancer prevention and control. A team of program members, led by Dr. Barcey Levy, was recently funded to apply this type of data to the Iowa research network as an approach to decrease disparities in colorectal cancer burden through partnership-building between the Iowa Cancer Consortium, IRENE, and the Holden Comprehensive Cancer Center. The resulting infrastructure will be established with a future plan to apply it to other screenable cancers and to lifestyle issues thereby increasing our capacity to perform community-based participatory research.
Newly funded grant (RC4 CA153493)
Research into approaches to decrease disparities in CRC burden through partnership-building
Iowa Cancer Consortium (ICC)
Iowa Research Network (IRENE)
Resulting infrastructure to be applied to other cancers and lifestyle issues (e.g., tobacco cessation, nutrition, physical activity)
Barcey Levy
Betsy Chrischilles
Tina Devery 14

15. Translational Research Registries
Prospective Registries
Collect and store peripheral blood, DNA, tumor
Rigorous clinical follow-up including quality of life
Supports biomarker discovery efforts and molecular epidemiology
Lymphoma (Iowa / Mayo Lymphoma SPORE)
Initiated 2002
4,013 subjects registered (Iowa & Mayo)
Melanoma and Sarcoma
Initiated 2008
476 subjects registered
Breast Cancer
Recently opened
Neuroendocrine
Initiated 2000
720 subjects registered

16. Molecular Epidemiology of Lymphoma
Correlation between outcome and
Vitamin D Levels
Complement Polymorphisms
Free Light Chain
DLBCL Survival
Cancer epi program members are participating in several ongoing projects involving the molecular epidemiology of lymphoma. These projects are interprogrammatic within the cancer center with Drs. Weiner and Link from the Immunology Program, Dr. Murry from the Signaling Program, and Drs. Cerhan, Chrischilles, Denburg, Smith, and myself. The projects include the Lymphoma SPORE, which has already been mentioned by Dr. Weiner, the SEER Program-based NHL Case-control Study, which has published extensively on etiologic and survival factors for NHL subtypes, and the Living with Lymphoma Study, which is an ongoing prognostic cohort study with follow-up for therapeutic response, myelotoxicity and neurocognitive abilities among Iowa residents recently diagnosed with lymphoma. The lower half of the slide highlights a recently published finding from the Lymphoma SPORE study population showing that circulating 25-hydroxyvitamin D insufficiency levels were associated with poorer overall survival for diffuse large B-cell lymphoma. Whether normalizing vitamin D levels in these patients improves survival will require testing in future trials. Correlations have also been identified in this population between survival and free light chains as well as with complement polymorphisms.
Drake et al, Vitamin D Insufficiency and Prognosis in Non-Hodgkin's Lymphoma, J Clin Oncol. 2010
Iowa Mayo Lymphoma SPORE
R01 Molecular Epi of NHL Survival
Jim Cerhan
Brian Link
George Weiner
Brian Smith 16

17. HCCC Clinical Research
Accrual
2010 Jan-Aug
(Projection for 2010 at current pace)
Investigator-Initiated Therapeutic Accruals 68
(102)
Total Therapeutic Accruals
205
(315)
805
(1380)
Non-Therapeutic Studies (estimated)

18. Sources for Funding NCI Other NIH
Non-Profit Organizations and Foundations
Pharmaceutical and Biotech Industry
Individual Philanthropy
Institutional Support

19. Annual NCI Funding to Iowa
$21,830,000
#27 in funding
#30 in population

20. National Cancer Institute Support for Clinical Research
Comprehensive Cancer Center
Community Clinical Oncology Program
Community Cancer Centers Program

21. What should be the role of the ICC in Cancer Research in Iowa?

22. Role of the ICC in Cancer Research
Basic T1 T2

23. Role of the ICC in Cancer Research
Basic Research
Advocacy T1
Advocacy
Coordination T2
Advocacy
Coordination
Collaboration
Coordination
Collaboration

24. What should be the role of the ICC in Cancer Research in Iowa?
Discussion