Revealing cancer’s deep evolutionary roots

A new way to look at cancer – by tracing its evolutionary roots to the dawn of multicellular life more than a billion years ago – could transform cancer therapy by linking cancer’s beginnings to the origin of life and the developmental processes of embryos. The new work, by researchers from Arizona State University and the Australian National University, appears in a special issue of the journal Physics World which is devoted to the physics of cancer.

The researchers, Paul Davies of Arizona State and his Aussie collaborator Charles Lineweaver, are both theoretical physicists and cosmologists with experience in the field of astrobiology. They turned to cancer research only recently, in part because of the creation at Arizona State of the Center for the Convergence of Physical Science and Cancer Biology.

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.

“We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells,” explains Davies. “It is rather like [the computer operating system] Windows defaulting to ‘safe mode’ after suffering an insult of some sort.” As such, he describes cancer as a throwback to an ancestral phenotype.

Their 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. The researchers are currently testing this prediction by comparing gene expression data from cancer biopsies with phylogenetic trees going back 1.6 billion years.

But if Davies and Lineweaver are right, why hasn’t evolution eliminated the ancient cancer subroutine?

“Because it fulfills absolutely crucial functions during the early stages of embryo development,” Davies suggests. “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. “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.

The new theory could provide clues to future treatments. For example, when life took the step from single cells to multicellular assemblages, Earth had low levels of oxygen. Similarly, 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 speculate 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.

“It is clear that some radically new thinking is needed,” Davies said in conclusion. “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.”

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Source: Arizona State University

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