New atavistic model shows role of ancient genes in the spread of cancer
From:
ARIZONA STATE UNIVERSITY
May 20, 2021 -- In spite of decades of
research, cancer remains an enigma. Conventional wisdom holds that cancer is
driven by random mutations that create aberrant cells that run amok in the
body.
In a new paper published this week in
the journal BioEssays, Arizona and Australian researchers challenge
this model by proposing that cancer is a type of genetic throwback, that
progresses via a series of reversions to ancestral forms of life. In contrast
with the conventional model, the distinctive capabilities of cancer cells are
not primarily generated by mutations, the researchers claim, but are
pre-existent and latent in normal cells.
Regents' Professor Paul Davies, director
of Arizona State University's Beyond Center for Fundamental Concepts in Science
and Kimberly Bussey, cancer geneticist and bioinformatician from the Precision
Medicine Program at Midwestern University, Glendale, Ariz., teamed up with
Charles Lineweaver and Anneke Blackburn at the Australian National University
(ANU) in Canberra to refine what they call the Serial Atavism Model (SAM) of
cancer. This model suggests that cancer occurs through multiple steps that
resurrect ancient cellular functions.
Such functions are retained by evolution
for specific purposes such as embryo development and wound healing, and are
usually turned off in the adult form of complex organisms. But they can be
turned back on if something compromises the organism's regulatory controls. It
is the resulting resurrection steps, or atavistic reversions, that are mostly
responsible for the ability of cancer cells to survive, proliferate, resist
therapy and metastasize, the researchers said.
Davies and Bussey are also members of
ASU's Arizona Cancer Evolution Center (ACE) which seeks to understand cancer,
not just in humans, but across all complex species, in the light of
evolutionary processes.
"Cancer research has been
transformed in recent years by comparing genetic sequences across thousands of
species to determine gene ages," Davies said. Just as geologists can date
rock strata, so geneticists can date genes, a technique known as
phylostratigraphy.
"The atavistic model predicts that
the genes needed for cancer's abilities are mostly ancient - in some cases
little changed over billions of years," Davies added.
Lineweaver explained, "In biology,
nothing makes sense except in the light of evolution, and in the case of cancer
nothing makes sense except in the light of the deep evolutionary changes that
occurred as we became multicellular organisms."
"The atavistic model of cancer has
gained increasing traction around the world," added Bussey. "In part,
this is because it makes many predictions that can be tested by
phylostratigraphy, unlike the conventional somatic mutation theory."
Blackburn, a cancer biologist in ANU's
John Curtin School of Medical Research, agreed.
"Appreciation of the importance of
gene ages is growing among oncologists and cancer biologists," she said.
"Now we need to use this insight to develop novel therapeutic strategies.
A better understanding of cancer can lead to better therapeutic outcomes."
https://www.eurekalert.org/pub_releases/2021-05/asu-cts051921.php
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