Everything Else
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Transcript of Everything Else
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 AnalysisRed = 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 AnalysisRed = 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 AnalysisRed = 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
COX2ERG
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
Prob
abili
tyProbability of Being Free of
Lung Metastases
p<0.0001
Years of Observation
= Lung Metastasis Signature = LMS
LMS NegativeLMS 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
Tum
or v
olum
e (m
m3)
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
0100200300400500600700800
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
Tum
our v
olum
e (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.