Everything Else What is Cancer? Biology

Part 1: Biology

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

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

Modified from William Gerald

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

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

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

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< Years of Observation = Lung Metastasis Signature = LMS LMS Negative LMS Positive 82 MSKCC Patients Cancer Cell Lines Ability to Generate Lung Metastases in Mice Low Medium High

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

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

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

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

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

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

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

Seeding sanctuary sites may create reservoirs for feeding future distant metastases

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

Arbitrary (Arithmetic) Time Scale Cubic Centimeters Self-Seeding Explains Gompertzian Growth

Magnetic Resonance Image of Human Breast with Cancer

Many New Targets for Therapy

Part 2: Everything Else

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

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

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

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.”

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

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