Cancer 101
One persons view....
Andrew Thorburn
Some things to bear in mind
about Cancer
• Second leading cause of death in the western world. Rapidly
becoming more and more important cause of death in
developing world.
• Cancer rates are rising (primarily caused by increasing life span)
although mortality is decreasing.
• Compared with progress for other major killers-e.g.
cardiovascular disease, progress against cancer has been dismal.
• However, we have seen significant improvements in survival for
some tumor types (e.g. testicular cancer, children’s leukemias,
some breast cancers), little progress for others (e.g.
glioblastoma, lung cancer, pancreatic cancer).
Development of Cancer
cell growth = cell death
Activate oncogenes
Inactivate tumor suppressors
cell growth > cell death
cell death < cell growth
Most Human Cancers probably
take decades to develop
Suppose we were able to delay the whole process by just 2-3 fold?
B Vogelstein et al. Science 2013;339:1546-1558
How to deal with Cancer...
• Prevent as much cancer as possible (probably about
half of cancer mortality can be prevented just with
things we already know about).
• Detect it early when its easier to deal with (but be
clever enough to ignore cancers that we really
shouldn’t be trying to treat).
• Effectively treat the rest - ideally using personalized
treatments that have limited toxicities and side effects.
• After you’ve had cancer get the optimal support and
care to ensure that CA survivorship is a good
experience
Cancers often have lots of mutations.... and different ones add on
new (often bad) behaviors to the tumor cells
Published by AAAS
B Vogelstein et al. Science 2013;339:1546-1558
Cancers often have lots of
mutations....
But the important ones
that drive tumor growth
seem to be in about a
dozen signaling pathways
that control cell fate, cell
survival & growth and
maintenance of the
genome. Some tumor
types have more of these
“drivers” than others
Published by AAAS
B Vogelstein et al. Science 2013;339:1546-1558
Hallmarks of Cancer
9
Prevention Strategies
• Change behaviors that we know lead to
cancer: tobacco, obesity, diet, exercise, sun
exposure, nasty chemicals etc.
• Are there other important prevention
strategies still out there waiting to be found
or is it just a matter doing what we know we
should do already?
Detection Strategies
• New technologies may allow us to detect cancer at
its earliest stages--can we do for other tumors what
we can do for colon cancer where early detection can
allow us to find and destroy tumors before they are
bad?
• Could there be a regular, reliable blood test to tell
you if you’ve got tumor cells lurking in your body?
• But how do we discriminate between the bad
cancers and the ones we can safely ignore--will
prostate CA where we may often actually over-treat
people be the model?
Treatment
•What do we do if prevention didn’t work and
early detection didn’t catch it before it was a
real tumor?
A short (and incomplete) history of cancer
treatment...
• ~1600 BCE--Egypt. Try to treat breast cancer by
cauterization using “fire drill”--conclusion ”there is no
treatment”
• ~400 BCE--Greece. Hippocrates- no effective treatment,
better to not try to treat cancer.
• ~200 CE--Rome. Galen cancer caused by “unbalanced
humors”--patient incurable, except in rare cases of breast
cancer where the complete tumor was removed
• mid 18th Century. John Hunter-”father of scientific
surgery”--surgery can cure cancer if you remove all the
tumor.
• early 1900s. Use X-rays/radiation to kill cancer cells.
• 1940s. Louis Goodman & Alfred Gilman: use nitrogen
mustard to treat lymphoma. Sidney Farber--kill cancer cells
with chemotherapy that blocks essential processes in a cell.
• 1960s-1980s. Combine chemotherapy; significant progress
with some tumors (e.g. pediatric ALL, testicular cancer).
• late 1990s. Improved use of radiation and traditional
chemotherapy. Targeted therapy-go after the defects in the
tumor cells rather than just treating with toxic agents that
kill all cells (normal and tumor).
• 2000- Hundreds of new agents, most try to selectively
target tumor cells and avoid killing normal cells but usually
work for only some people.
New cancer drugs have lower success rates
than drugs to treat other diseases
Success defined as: % of drugs tested in
humans that were approved for use by
the FDA
95% of oncology drugs that are tested in
people fail, this doesn’t count the ones
that don’t even get into people!
Kamb et al. Nature Reviews Drug Discovery 6, 115–120 (February 2007)
Targeting the Hallmarks
If you get a drug that works, the
results can be spectacular
For most tumors, when drugs do work, they
only work for some people....
The good news:
Oct 2006
(baseline)
August 2007
(peak response)
Ross Camidge
The bad news: it stopped working
August 2007
(peak response)
Jan 2008
(regrowth
pelvic lesion)
...but not in all the tumors
August 2007
(peak response
in pelvis)
Jan 2008
(continuing response
in other lesions)
The way we hope cancer therapy is going...
Targeting the Hallmarks
23
Epidermal Growth Factor Receptor as an
example of a therapeutic target
EGFR Signaling (greatly simplified)
12
EGFR Signaling (simplified a bit less)
how do we decide on the best target?
Too many potential drug combinations
to make sense of?
Difficult to
make sense
of....But, a good
problem for us
to have!
Survivorship
•Will our treatments cause other problems?
Including other cancers?
•How do we ensure that after cancer people
live healthy (healthier!) happy lives?
Bottom Line
• Cancer is a hard problem – you’re really trying to kill off bits
of yourself and fighting natural selection
• But it’s not hopeless. We know how to prevent at least half of
it. It takes a long time for cancer to develop so there is usually
plenty of time when one could step in and deal with the
problem. We know cancer is a genetic problem but think
there are a core set of relatively few pathways that are
important– these are the targets that we are now going after.
But we need to know who to treat and find ways to get
around resistance.
• The only way to make real progress (after at least 3,500
years!) is by working together and dealing with every aspect
of the problem.