A new theory about cancer in contradiction with epigenetics is evolving.
A new theory about cancer and the evolution of this diseases was developed by Paul Davies, principal investigator at Arizona State University’s Center for Convergence of Physical Sciences and Cancer Biology. The articles published recently in Phys.org/news are here presented as a topic to collect different comments. You are all invited to participate in this discussion. Who is right, epigenetics or this evolutionary cancer theory?
With death rates from cancer have remained largely unchanged over the past 60 years, a physicist is trying to shed more light on the disease with a very different theory of its origin that traces cancer back to the dawn of multicellularity more than a billion years ago.
In this month’s special issue of Physics World devoted to the “physics of cancer”, Paul Davies, principal investigator at Arizona State University’s Center for Convergence of Physical Sciences and Cancer Biology, explains his radical new theory.
Davies was brought in to lead the centre in 2009 having almost no experience in cancer research whatsoever. With a background in theoretical physics and cosmology, he was employed to bring fresh, unbiased eyes to the underlying principles of the disease.
He has since raised questions that are rarely asked by oncologists: thinking about why cancer exists at all and what place it holds in the grand story of life on Earth.
His new theory, drawn together with Charles Lineweaver of the Australian National University, suggests that cancer is a throwback to an ancient genetic “sub-routine” where the mechanisms that usually instruct cells when to multiply and die malfunctions, thus forcing the cells to revert back to a default option that was programmed into their ancestors long ago.
“To use a computer analogy, cancer is like Windows defaulting to ‘safe mode‘ after suffering an insult of some sort,” Davies writes.
The result of this malfunction is the start of a cascade of events that we identify as cancer – a runaway proliferation of cells that form a tumour, which eventually becomes mobile itself, spreading to other parts of the body and invading and colonizing.
Orthodox explanations suppose that cancer results from an accumulation of random genetic mutations, with the cancer starting from scratch each time it manifests; however, Davies and Lineweaver believe it is caused by a set of genes that have been passed on from our very early ancestors and are “switched on” in the very early stages of an organism’s life as cells differentiate into specialist forms.
The pair suggests that the genes that are involved in the early development of the embryo – and that are silenced, or switched off, thereafter – become inappropriately reactivated in the adult as a result of some sort of trigger or damage, such as chemicals, radiation or inflammation.
“Very roughly, the earlier the embryonic stage, the more basic and ancient will be the genes guiding development, and the more carefully conserved and widely distributed they will be among species,” Davies writes.
Several research teams around the world are currently providing experimental evidence that shows the similarities between the expression of genes in a tumour and an embryo, adding weight to Davies and Lineweaver’s theory.
Davies makes it clear that radical new thinking is needed; however, just like ageing, he states that cancer cannot generally be cured but can be mitigated, which we can only do when we better understand the disease, and its place in the “great sweep of evolutionary history”.
Davies and Lineweaver are both theoretical physicists and cosmologists with experience in the field of astrobiology—the search for life beyond Earth. They turned to cancer research only recently, in part because of the creation at Arizona State University of the Center for the Convergence of Physical Science and Cancer Biology. The Center is one of twelve established by the National Cancer Institute to encourage physical scientists to lend their insights into tackling cancer.
The new theory challenges the orthodox view that cancer develops anew in each host by a series of chance mutational accidents. Davies and Lineweaver claim that cancer is actually an organized and systematic response to some sort of stress or physical challenge. It might be triggered by a random accident, they say, but thereafter it more or less predictably unfolds.
Their view of cancer is outlined in the article “Exposing cancer’s deep evolutionary roots,” written by Davies. It appears in a special July issue of Physics World devoted to the physics of cancer.
“We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells,” says Davies, an Arizona State University Regents Professor. “It is rather like Windows defaulting to ‘safe mode’ after suffering an insult of some sort.” As such, he describes cancer as a throwback to an ancestral phenotype.
The new theory predicts that as cancer progresses through more and more malignant stages, it will express genes that are more deeply conserved among multicellular organisms, and so are in some sense more ancient. Davies and Lineweaver are currently testing this prediction by comparing gene expression data from cancer biopsies with phylogenetic trees going back 1.6 billion years, with the help of Luis Cisneros, a postdoctoral researcher with Arizona State University’s Beyond Center.
But if this is the case, then why hasn’t evolution eliminated the ancient cancer subroutine?
“Because it fulfills absolutely crucial functions during the early stages of embryo development,” Davies explains. “Genes that are active in the embryo and normally dormant thereafter are found to be switched back on in cancer. These same genes are the ‘ancient’ ones, deep in the tree of multicellular life.”
The link with embryo development has been known to cancer biologists for a long time, says Davies, but the significance of this fact is rarely appreciated. If the new theory is correct, researchers should find that the more malignant stages of cancer will re-express genes from the earliest stages of embryogenesis. Davies adds that there is already some evidence for this in several experimental studies, including recent research at Harvard University and the Albert Einstein College of Medicine in New York.
“As cancer progresses through its various stages within a single organism, it should be like running the evolutionary and developmental arrows of time backward at high speed,” says Davies.
This could provide clues to future treatments. For example, when life took the momentous step from single cells to multicellular assemblages, Earth had low levels of oxygen. Sure enough, cancer reverts to an ancient form of metabolism called fermentation, which can supply energy with little need for oxygen, although it requires lots of sugar.
Davies and Lineweaver predict that if cancer cells are saturated with oxygen but deprived of sugar, they will become more stressed than healthy cells, slowing them down or even killing them. ASU’s Center for the Convergence of Physical Science and Cancer Biology, of which Davies is principal investigator, is planning a workshop in November to examine the clinical evidence for this.
“It is clear that some radically new thinking is needed,” Davies states. “Like aging, cancer seems to be a deeply embedded part of the life process. Also like aging, cancer generally cannot be cured but its effects can certainly be mitigated, for example, by delaying onset and extending periods of dormancy. But we will learn to do this effectively only when we better understand cancer, including its place in the great sweep of evolutionary history.”