Everything Else

1. Everything Else Biology What is Cancer?

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

9. Modified from William Gerald

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

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

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

13. SPARC IL13RA2 MMP1 ERG COX2 CXCL1 MMP2 ID1 RARRES3 EFEMP1 MANT2 LY6E 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Cancer Cell Lines Ability to Generate Lung Metastases in Mice Low High Medium = Lung Metastasis Signature = LMS 82 MSKCC Patients LMS Negative LMS Positive Probability of Being Free of Lung Metastases p<0.0001 Years of Observation Minn, Gupta et al.,Nature 2005

14. 400 300 200 100 0 Lung Metastasis Genes Are Associated with Faster Growth in the Mouse “Breast” 800 ** 700 LMS High Tumor volume (mm3) 600 LMS Medium 500 LMS Low ** LMS Low Days post-injection 0 10 20 30 40 50 Minn, Gupta et al.,Nature 2005

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. Seeded tumours Unseeded tumours 800 IC injection of LM2 cells p<0.0001 600 n=14 p<0.005 400 Tumour volume (mm3) n=15 200 0 0 10 20 30 40 50 Days after tumour initiation Self-seeding of mammary tumors by circulating cancer cells Promotion of tumor growth … by a minority of seeding cells Mi-Young Kim

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

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

23. 100 1 Self-Seeding Explains Gompertzian Growth 0.01 Cubic Centimeters 0.0001 0.000001 0.00000001 0 20 40 60 80 100 Arbitrary (Arithmetic) Time Scale

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.