1. Everything Else What is Cancer? Biology

2. Part 1: Biology

3. The Biology of Cancer Excess Cell Growth Invasion into Surrounding Tissue Spread to Other Parts of the Body (Called Metastasis)

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8. Modified from William Gerald DNA is organized in genes, which code RNAs, which code proteins, which do the work of the cell.

9. Modified from William Gerald

10. Gene A NormalCancer Microarray Analysis Red = Gene On Green = Gene Off Gene B Gene C Gene C* Gene A is a Tumor Suppressor Gene Modified from William Gerald

11. Gene A NormalCancer Microarray Analysis Red = Gene On Green = Gene Off Gene B Gene C Gene C* Gene B is Over-Expressed in Cancer Modified from William Gerald

12. Gene A NormalCancer Microarray Analysis Red = Gene On Green = Gene Off Gene B Gene C Gene C* Gene C is an Oncogene Modified from William Gerald

13. SPARC CXCL1 IL13RA2 MMP2 ID1 MMP1 COX2 ERG RARRES3 EFEMP1 MANT2 LY6E Minn, Gupta et al., Nature 2005 Probability of Being Free of Lung Metastases p<0.0001 Years of Observation = Lung Metastasis Signature = LMS LMS Negative LMS Positive 82 MSKCC Patients 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16 17 18 19 Cancer Cell Lines Ability to Generate Lung Metastases in Mice Low Medium High

14. Tumor volume (mm 3 ) Days post-injection ** Lung Metastasis Genes Are Associated with Faster Growth in the Mouse “Breast” Minn, Gupta et al., Nature 2005 500 600 700 800 01020304050 LMS High LMS Medium LMS Low

15. Seeding regional lymph nodes and seeding distant sites use similar (but not identical) genetic tools.

16. Seeds that have traveled to normal tissue in the organ of origin may later seed distant sites.

17. Seeding the tumor itself produces rapid growth, anaplasia, and “stem cells” disbursed throughout the mass

18. Mi-Young Kim Self-seeding of mammary tumors by circulating cancer cells Promotion of tumor growth … by a minority of seeding cells

19. Mi-Young Kim Self-seeding of mammary tumors by circulating cancer cells Seeding enhances tumor angiogenesis… and leukocyte infiltration

20. Does the primary tumor site act as a “sponge” for seeds?

21. Seeding sanctuary sites may create reservoirs for feeding future distant metastases

22. What is the Pattern of Growth of Cancer? Benjamin Gompertz, 1825 Norton et al., Nature, 1976

23. 0.00000001 0.000001 0.0001 0.01 1 100 020406080100 Arbitrary (Arithmetic) Time Scale Cubic Centimeters Self-Seeding Explains Gompertzian Growth

24. Magnetic Resonance Image of Human Breast with Cancer

25. Many New Targets for Therapy

26. Part 2: Everything Else

27. Things I’ve Learned If you gather all the information you need, decisions make themselves.

28. Things I’ve Learned Make sure you communicate “I’m here to get better,” not “Whatever you do, don’t hurt me.”

29. Things I’ve Learned If you don’t like your doctor, most likely he/she doesn’t like you.

30. Things I’ve Learned When you ask “What is the best therapy for me?” watch out for “What I have to offer you is this.”

31. Things I’ve Learned When you think about your future, think about positive things. Don’t forget the moment.

32. Things I’ve Learned You are more than your body. Make sure that you do something just for yourself every day.