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)

?

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

Normal

Cance

r

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

Normal

Cance

r

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

Normal

Cance

r

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

RARRES3EFEMP1MANT2LY6E

Minn, Gupta et al., Nature 2005

0

0.2

0.4

0.6

0.8

1

0 2 4 6 8 10 12

LMFS

Pro

bab

ilityProbability

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 14 15 16 17 18 19

Cancer Cell Lines

Ability to Generate Lung Metastases in Mice

Low Medium High

Tu

mo

r v

olu

me

(mm

3)

Days post-injection

**

**

Lung Metastasis Genes Lung Metastasis Genes Are Associated with Faster Growth in the Mouse “Breast”Are Associated with Faster Growth in the Mouse “Breast”

Minn, Gupta et al., Nature 2005

0

100

200

300

400

500

600

700

800

0 10 20 30 40 50

LMS High

LMS Medium

LMS Low

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

Tu

mo

ur

volu

me

(m

m3 )

Days after tumour initiation

Seeded tumours

Unseeded tumours

p<0.0001

n=14

n=15

IC injectionof LM2 cells

p<0.005

10 20 30 40 50

200

400

600

800

00

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

0.00000001

0.000001

0.0001

0.01

1

100

0 20 40 60 80 100

Arbitrary (Arithmetic) Time Scale

Cub

ic C

entim

eter

s

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.