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What is Cancer?
Updated April 2013
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What is Cancer?
Confidential & Proprietary
What is Cancer?
•  The simple answer to this question is:
–  “Cancer is a group of diseases characterized by uncontrolled growth
and spread of abnormal cells”
American Cancer Society
–  “A malignant tumor of potentially unlimited growth that expands
locally by invasion and systemically by metastasis”
Webster’s Ninth New Collegiate Dictionary
•  From a scientific perspective, cancer is a result of cumulative
alterations or mutations in a cell’s DNA allowing for growthpromoting behavior
–  While the exact mechanisms resulting in cancer are still being
elucidated, it may be easier to think of cancer as a consequence of a
chaotic process, a combination of Murphy’s Law and Darwin’s Law:
•  Anything that can go wrong will, and in a competitive environment, the best
adapted cells survive and prosper What is Cancer? • April 2013
Slide 2
What is Cancer?
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Six Acquired Capabilities of Cancer
Self-­‐sufficiency in growth signals Insensi-vity to an--­‐growth signals Tissue invasion & metastasis Limitless replica-ve poten-al Most cells require an external Cancer signal Cancer Cancer cells to cells ini0ate gcain ells develop tihe gnore growth. ability the to Cancer cells bypass the Cancer c
ells o
vercome the Cancer Cancer ability extracellular s0mulate tco ells invade bclood an signals gaenerate vdjacent essel that normal c
ell d
eath o
r s
uicide limita0ons o
n to ell dalt ivision their 0ssue would forma0on own ans ormally pwro-­‐growth ell acs psrovide hend scignals
oell ut Cell mechanisms (
“apoptosis”)
(around 7
0 0
mes)
“pioneer” nutrients division
cells to tthe o etstablish umor distant tumors Evading apoptosis Sustained angiogenesis Adapted from Hanahan, Cell, 2000.
What is Cancer? • April 2013
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What is Cancer?
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Parallel Tumorigenesis Pathways
Self-­‐sufficiency in growth signals Evading apoptosis Limitless replica0ve poten0al Insensi0vity to an0-­‐growth signals Sustained angiogenesis Tissue invasion & metastasis Adapted from Hanahan, Cell, 2000.
What is Cancer? • April 2013
Slide 4
What is Cancer?
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Genetic Factors
•  Genetic factors have been shown to play an increasingly
important role in the development and progression of
some malignancies
•  Some of the key genetic factors include:
– Gene Mutations: either inherited or acquired
•  Oncogenes: increase or enhance tumor development (e.g., HER2, ras)
•  Tumor suppressor genes: decrease activity of tumor development (e.g.,
p53, pRb)
•  Cell regulatory genes: influence key cellular functions (apoptosis, DNA
repair), (e.g., bcl-2, PTEN)
•  Current thinking is that gene mutations occur prior to
the start of “oncogenesis” and then accumulate
throughout the development and progression of the
disease
What is Cancer? • April 2013
Slide 5
What is Cancer?
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Impact of Epigenetics
•  Epigenetics are
changes in gene
expression without
any changes in a
patient’s DNA
•  These processes
include histone
modifications and
DNA methylation •  The changes can
influence gene
expression,
apoptosis, and
cellular growth
What is Cancer? • April 2013
Slide 6
What is Cancer?
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The Reality of the Situation
•  However, none of the many proposed theories of the
primary cancer mechanism have been proven to be
correct
– In fact, it is possible there are are many mechanisms for the
development of cancer
– This makes our jobs seeking significant advances in treatment
much more difficult since any major new therapy may be
overcome by the broad variety of mechanisms in play in
oncogenesis
What is Cancer? • April 2013
Slide 7
Why Cancer?
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The Huge Economic Burden of Cancer
•  The economic cost of cancer exceeds that of any other disease
–  Only accounts for disability and premature death, no direct medical costs
Sources: American Cancer Society, Livestrong, and World Health Organization
What is Cancer? • April 2013
Slide 8
Why Cancer?
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Major Causes of U.S. Deaths
•  Since 1960, cancer has been the second leading cause of death in the U.S.
–  In 2010, cancer was estimated to be the leading cause of death worldwide; while this might not
be the case in the U.S., it is expected to eventually surpass cardiovascular disease which has
been on a continual decline Leading Causes of Death (per 100,000), U.S., 1960-2010
400.0
350.0
300.0
250.0
Cardiovascular Disease
Cancer
Cerebrovascular Diseases
Chronic Lower Respiratory Diseases
Accidents
Influenza/Pneumonia
Diabetes Mellitus
200.0
150.0
100.0
0.0
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
50.0
Source: NCHS, Leading Causes of Death, 1960-2010.
What is Cancer? • April 2013
Slide 9
Why Cancer?
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Cancer Affects Everyone
•  Cancer affects everyone in the U.S.
–  Men have almost a 1-in-2 chance of developing a malignant cancer with almost a 1in-4 chance of dying from cancer
–  Women have more than 1-in-3 chance of developing a malignant cancer with slightly
less than 1-in-5 chance of dying from cancer
Risk of Developing Cancer
50.0%
45.0%
Risk of Dying from Cancer
44.8%
41.2%
38.2%
40.0%
35.0%
30.0%
25.0%
22.9%
20.9%
19.5%
20.0%
15.0%
10.0%
5.0%
0.0%
Both Sexes
Males
Females
Source: Probability of Developing or Dying of Cancer Software,Version 6.6.1. Surveillance Research Program, Statistical Methodology and Applications Branch, National Cancer Institute, 2012. http://surveillance.cancer.gov/devcan.
What is Cancer? • April 2013
Slide 10
Isn’t it Time You Had
an Epiphany?
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Main Number: +1-650-242-4626
Steve Clark
Peter
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