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Cancer and Evolution
Cancer and Evolution
Importance
i.
Understand cancer development at the level of the species as well as the level of
the cells and tissues
ii.
New insights to cancer prevent and treatment
Older humans less likely to reproduce and contribute to the gene pool
Hence, less selective pressure to maintain tissues and suppress cancers in old age
Result general decline in tissue structure and function and increase cancer rates as
human ages
Antagonistic pleiotropy some processes which are important in organismal fitness in
youth may actually contribute to tissue decline and increased cancer in old age
Evolution has in effect weighed the costs and benefits of somatic tissue maintenance and
tumor suppression, favoring a strategy that maximizes reproductive success.
Carcinogens increase genetic mutations (genetic diversity) and also alters the
environment (selective pressures)
Modern humans encounter many new chemical and physical agents to which we have not
evolve effective protective mechanisms
Advanced cancers have higher mutation rates, multiple selective hurdles, variable
microenvironments and increased numbers of cell generations (NB: Cancers consist of
from a billion to a 1000 billion (1012) cells, resulting from 100s to 1000s of cell
generations , which is on the scale of the number of generations spanning the entire
evolutionary history of Homo sapiens).
Great genetic variability
o Ample opportunities to adapt to change and evolution of diverse types
Chemotherapy and radiation are selective pressures selecting for clones that can best
survive resistance
Postulated a fitness cost to chemotherapy
o Chemotherapy sensitive cells are often more fit and actually suppress the growth
of less fit chemotherapy resistant clones
o Hence, try to treat and debulk the tumour with chemotherapy but still maintain a
chemo-sensitive population to oppose the growth of chemo-resistant clones =
sinusoid growth curve
Targeted therapy
o Problem with development of resistance due mutation activating alternate
oncogene
o Develop combination therapies up front that target both the driving oncogene and
anticipated escape mechanisms
Prevent metastatic events
o Rapidly dividing mass of cells result in acidic and low oxygen environment
o This promotes evolution of clones with ability to migrate to greener pastures
o Theoretically, re-oxygenating tumours can remove this selective pressure,
prevent the evolution of clones with a more motile phenotype and decrease the
possibility of metastasis.
7. Conclusion
a) The evolution of multi-cellular animals necessitated the acquisition of potent tumour
suppressive mechanisms, which operate at levels of individual cells, tissue organization
and the whole body to limit cancers.
b) Cancer follows an evolutionary trajectory, with acquisition of mutations that allow the
cancer cells to adapt and succeed in the face of selective barriers.
c) Carcinogenic contexts, from chemicals to radiation to aging, can promote cancer
evolution both by increasing mutation frequency and by promoting selection for adaptive
mutations
d) Cancers respond to insults with selection for the clones that are most fit under that
context, such as during chemotherapy.
e) By understanding cancer from an evolutionary and ecological perspective, we should be
able to design more rational therapeutic approaches that manipulate cancer's evolutionary
trajectories for patient benefit.