1. Emerging Issues in Cancer Control: The Perspective from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Martin D. Abeloff, M.D. Director – SKCCC November 12, 2003

2. A Comprehensive Cancer Center Designated by the National Cancer Institute NIC CCC THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS HOPKINS

3. Mission  To decrease the mortality and morbidity from cancer  To excel in cutting edge basic, clinical and translational research  To provide the full range of highest quality, affordable, preventive, diagnostic, and therapeutic services  To be a leader in education  To demonstrate respect and provide support for faculty and staff while fulfilling the Center’s mission

4. Research Accomplishments The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Elucidation of the molecular steps in the development of colon cancer  Identification of markers of risk for development of cancer  Therapies for prevention of cancer

5. Research Accomplishments The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins - (continued)  Discovery and development of new anti-cancer therapies including drugs, vaccines, and bone marrow transplantation  New approaches to supportive and palliative care

6. Cancer Center Membership by Departments (253 Members*/27 Depts.) Other includes: Anes, Bio Eng, Comp Med, Derm, Microbio, Mol Bio, Neur, Peds, Pharm, Phy, Radiol, SON *18 Pending

7. Normal Small Adenoma Cancer Large Adenoma Metastasis APC/  -catenin TGF-  RII/ Smad4 p53 K-Ras PRL-3 Chromosomal or Microsatellite Instability Vogelgram – early detection 30 to 40 years

8. Problems with Detecting APC Mutations in Fecal DNA 1. Human DNA small fraction of fecal DNA 2. APC mutations are heterogeneous 3. Mutant APC genes <1% of WT genes 4. Contaminants in feces

9. Problems Comparison with widely used screening tests Mammography Sensitivity 75-88% Specificity 83-98% Pap Smear 65-80% 90-98% PSA 40-60% 88-94% APC/fecal DNA 70% >99%

10. CA Cancer J Clin 2003;53:5-26

11. Decrease in UK and USA Breast Cancer Deaths from 1987 to 1997 Decrease in death rate per 100,000 women (Age Group) 20-4950-6970-79 UK 22%22%12% USA 19%18% 9% “This substantial reduction in national mortality rates has come not from a single research breakthrough but from the careful evaluation and adoption of many interventions, each responsible on its own for only a moderate reduction in breast cancer mortality” Peto et al:Lancet 2000:355:1822

12. Trends in Breast Cancer in Five-Year Survival Rates (%) by Race and Year of Diagnosis 1974-1998 1974-76 1983-85 1992-98 White 757988 African-American 636373 All Races 757886

13. Key Factors Leading to Changes in Management of Breast Cancer  Marked increase in understanding of biology of breast cancer (molecular and cellular biology)  Development of clinical research centers, networks, infrastructure, and methodologies  Improvements and innovations in surgery and radiation therapy  New drugs and combinations: cytotoxic, endocrine, targeted biologic therapies  Patient autonomy  Patient advocacy movement

14. The Future of Cancer Research and Care  Greater emphasis on prevention Changes in life style – nutrition, exercise, tobacco, alcohol Chemoprevention  Screening and early detection Molecular markers Molecular imaging  Molecular targeting of cancer as basis of therapy and prevention

15. The Future of Cancer Research and Care ( cont.)  Multimodality therapy will continue to be central theme  Incremental gains  Not simply a biomedical challenge – Societal imperatives!  Integration with State initiatives in particular the State cancer plan

16. MD Cancer Plan Chapter 13: Cervix Cancer Objective 6  Conduct a follow-back study to determine factors that contribute to women developing or dying from invasive cervical cancer….  Establish and maintain mechanisms to monitor the proportion of cervical cancer cases and deaths attributable to failures of detection….

17. CRF Research Grants at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Connie Trimble: Center for Cervical Studies – Proportion without timely screening – HPV status follow-up – Case management – Vaccine development Kristen Kjeruff: Racial Disparities among Cervical Cancer Patients – Patient characteristics – Treatment outcomes

18. MD Cancer Plan Chapter 8 Environmental Health and Cancer Objective 2 – Improve data collection and carcinogen exposure assessment Objective 3 – Enhance collaboration between academic research institutions and State and local public health departments

19. CRF Research Grants at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Tim Buckley and Tom Burke: Cancer Prevention in Maryland through Risk Characterization – Identify environment-related cancers – Quantify human risk from monitoring data – Test correlations and calculate environmental contribution to cancer occurrence – Tracking projects with MD health officials underway Anthony Alberg: The Joint Influence of Active and Passive Smoking on Cancer Incidence – Quantification of active and passive smoking risks in a western MD population