New theory uncovers cancer's deep evolutionary roots

http://www.eurekalert.org/pub_releases/2013-07/asu-ntu071113.php

Public release date: 11-Jul-2013
Contact: Skip Derra
Arizona State University

Tracing cancer back to the dawn of multicellularity could explain its mysterious properties and transform therapy

TEMPE, Ariz. -- A new way to look at cancer -- by tracing its deep evolutionary roots to the dawn of multicellularity more than a billion years ago -- has been proposed by Paul Davies of Arizona State University's Beyond Center for Fundamental Concepts in Science in collaboration with Charles Lineweaver of the Australian National University. If their theory is correct, it promises to transform the approach to cancer therapy, and to link the origin of cancer to the origin of life and the developmental processes of embryos.

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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.

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