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Printable Handouts
Navigable Slide Index
- Introduction
- Why do most cancers develop after the age of 50?
- Different factors
- Cancer arises by clonal selection
- Current paradigm: cancer incidence is limited by the occurrence of oncogenic mutations
- Evolution – driven by the occurrence of the right mutations over time?
- Oncogenic mutations in young healthy stem cell populations typically reduce cellular fitness
- Mutation rates
- Peto’s paradox – large and long-lived animals do not develop more cancers
- Another problem
- What about breast cancer, testicular cancers, childhood cancers, and lymphomas in young people?
- Aging theory
- Evolved tumor suppressive mechanisms (1)
- Evolved tumor suppressive mechanisms (2)
- Life is not linear
- Our physiological decline not linear - why does it matter for cancer?
- So how are tissues maintained?
- Why does it matter?
- Adaptive oncogenesis
- High stem cell fitness opposes somatic evolution, and thus promotes the status quo
- But what is the evidence for differential selection for somatic mutations depending on context?
- Specific oncogenic events are selected for within aged hematopoietic contexts dependent on inflammation
- Model of cancer incidence
- The conventional paradigm
- Recent examples of context-dependent oncogenic adaptation in humans
- Our bodies become riddled with “oncogenic” mutations as we age – what are the implications?
- There are many risk factors for cancer beyond old age
- Decoy fitness peaks, tumor suppression, and aging
- Implications
- Aging is associated with increases in the risks of multiple diseases
- Efforts to prevent and treat cancer should converge with similar efforts to prevent other aging-associated diseases
- What I have not covered (1)
- Intratumor heterogeneity
- What I have not covered (2)
- Adaptive therapy
- Current status
- Acknowledgements
Topics Covered
- Development of cancer with age
- Evolution of oncogenic mutations
- Tumor suppressive mechanisms
- Adaptive oncogenesis
- Tissue maintenance
- Risk factors for cancer
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
DeGregori, J. (2022, January 30). Connecting aging and cancer through the lens of evolution [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/ODEE3317.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. James DeGregori has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Genetics & Epigenetics
Transcript
Please wait while the transcript is being prepared...
0:00
Hello everyone, I'm James DeGregori.
I'm a professor at the University of Colorado Cancer Center and I'll be
talking about how we can connect aging and cancer through the lens of
evolution and how this alternative understanding of
the formation of cancers can be beneficial to both prevention and treatment.
0:22
One thing that most of us will appreciate is that
about 90 percent of cancers develop after the age of 50.
The real question is why?
0:33
For the conventional point of view,
and probably the view that you've read about in your textbooks this is
really requires time, cell divisions, exposures such as from
smoking and our underlying genetics and all of
these different factors basically contribute to
one major causative factor and that is mutations.
The conventional point of view holds that it's the mutations that drive cancers and there's
0:59
been this classic understanding of cancer evolution for
the last 50 or plus years whereby cancer arises by clonal selection.
We start with an initiating mutation,
what we would call an oncogenic mutation,
it happens in a single cell shown here in red and this will then lead to the expansion of
that clone because that mutation is thought to
confer some advantage to the cell relative to its peers.
After that clone expands,
you're going to increase the odds of the next mutation which is
shown with a little green quadrant which then provides
a further advantage allowing that clone to competitively
expand even beyond the initial red clone and so forth.
From this understanding we can appreciate how
a cancer can accumulate multiple mutations within
the same clone that provide
the different characteristics or what we call phenotypes of the cancer,
and it's these characteristics of the cancer that of
course cause so much damage and death to humans.