Download Modified from William Gerald

What is Cancer?
Everything
Else
Biology
Part 1: Biology
The Biology of Cancer
• Excess Cell Growth
• Invasion into Surrounding Tissue
• Spread to Other Parts of the Body
(Called Metastasis)
?
DNA is organized
in genes, which
code RNAs, which
code proteins,
which do the work
of the cell.
Modified from William Gerald
Modified from William Gerald
Microarray Analysis
Red = Gene On
Green = Gene Off
Gene A
Gene B
Gene C
Gene C*
Gene A is a Tumor Suppressor Gene
Modified from William Gerald
Microarray Analysis
Red = Gene On
Green = Gene Off
Gene A
Gene B
Gene C
Gene C*
Gene B is Over-Expressed in Cancer
Modified from William Gerald
Microarray Analysis
Red = Gene On
Green = Gene Off
Gene A
Gene B
Gene C
Gene C*
Gene C is an Oncogene
Modified from William Gerald
Ability to Generate
Lung Metastases in Mice
Low
Medium
High
SPARC
IL13RA2
MMP1
ERG
COX2
= Lung Metastasis Signature = LMS
82 MSKCC Patients
CXCL1
MMP2
LMS Negative
LMS Positive
ID1
1
Probability
0.8
RARRES3
EFEMP1
MANT2
LY6E
Probability of
0.6
Being Free
of Lung 0.4
Metastases
p<0.0001
0.2
0
0
2
4
6
8
10
12
Years of Observation
LMFS
1 2 3 4 5 6 7 8
9 10 11 12 13 14
15 16 17 18 19
Cancer Cell Lines
Minn, Gupta et al., Nature 2005
Tumor volume (mm3)
Lung Metastasis Genes
Are Associated with Faster Growth in the Mouse “Breast”
800
700
600
500
400
300
200
100
0
LMS High
**
LMS Medium
LMS Low
**
LMS Low
0
10
20
30
40
Days post-injection
50
Minn, Gupta et al., Nature 2005
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
Self-seeding of mammary tumors by circulating cancer cells
Promotion of tumor growth
Seeded tumours
800
Tumour volume (mm3)
… by a minority of seeding cells
Unseeded tumours
IC injection
of LM2 cells
600
p<0.0001
n=14
p<0.005
400
200
n=15
0
0
10
20
30
40
50
Days after tumour initiation
Mi-Young Kim
Self-seeding of mammary tumors by circulating cancer cells
Seeding enhances tumor angiogenesis
… and leukocyte infiltration
Mi-Young Kim
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
Cubic Centimeters
100
1
Self-Seeding Explains
Gompertzian Growth
0.01
0.0001
0.000001
0.00000001
0
20
40
60
80
Arbitrary (Arithmetic) Time Scale
100
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.