Putting the Brakes On Cancer’s Evolution

I arrived this afternoon in San Francisco, so that I can participate in an exceptional sort of meeting: the 2nd International Biannual Evolution and Cancer Conference. Friday night I’ll be giving a talk about some of the lessons we can learn about cancer from other animals (details at the end of this post), but for the most part, I’ll be on the receiving end, learning about the latest research at this fascinating crossroads.

Cancer is fundamentally an evolutionary disease, as I explained in a 2007 article for Scientific American. By which I mean that cancer is an inevitable menace to any multicellular organism, which has led the evolution of lots of anti-cancer defenses in our biology. But each time cancer emerges, it plays out in an evolutionary process, a natural selection happening within our own bodies. As new mutations arise, certain cancer cells fare better than others. Tumors evolve, as their cells gaining all sorts of abilities–such as attracting new blood vessels to feed their voracious appetites–that their ancestors didn’t have.

A number of scientists have been exploring ways to approach the battle against cancer, informed by an understanding of how evolution works. It’s a promising idea, but it demands answering a lot of basic questions before too many patients start getting treatments influenced by Darwin. Today, by happy coincidence, one of the organizers of the meeting I’ll be at, Carlo Maley of UCSF, and his colleagues have published a paper on just this sort of work. Their research suggests that one way to fight cancer is to put the brakes on its evolution.

For a decade, evidence has been emerging that a daily dose of aspirin can lower the death rate of several kinds of cancer. Yet the reason why it does so has been locked in a black box. Maley and his colleagues set out to understand that reason. They focused on one particular kind of cancer aspirin can help, which strikes the esophagus. People sometimes develop a pre-cancerous condition called Barrett’s esophagus, in which fast-growing, irregularly shaped cells start to grow on the esophagus lining. Those cells sometimes give rise to full-blown cancer cells, causing esophageal adenocarcinoma.

For years, Maley and his colleagues have been studying a large group of patients with Barrett’s esophagus. For this particular research, they wanted to see how the cancer progressed in people both while they were taking aspirin and while they weren’t. They selected thirteen people from the study and examined biopsies from their esophagus taken over the course of as long as 20 years.

The scientists then looked at a sample of cells from each biopsy and scanned their DNA. This information allowed them to draw evolutionary trees for the cancer cells, so that they could see how the cells had evolved from a common ancestor. By following the branches of the tree, the scientists could identify the new mutations, broken chromosomes, and other abnormalities that arose along the way. They could then calculate the rate at which those abnormalities appeared.

The results were pretty clear. Aspirin cut the rate of new abnormalities in the cancer cells–by a factor of ten. Natural selection only works if there is variation to select from. The more variation there is, the faster it transform a population–whether that population is army ants, marigolds, or cancer cells. Maley’s study suggests that aspirin somehow preserves the integrity of cancer cell DNA and thereby blocks their evolution.

One intriguing finding of the new study is that in many cases, the cells didn’t accumulate their mutations gradually, but in bursts. Could this be an inner punctuated equilibrium? A study on only 13 people can only be preliminary–a dip of the toe into a lake of new ideas. But it also shows just how rich those ideas can be.

[I will be speaking at 7 pm Friday June 14 at Robertson Auditorium on the UCSF Mission Bay Campus at 1675 Owens Street. More details are here. The rapper Baba Brinkman will be performing after my talk. The whole shebang is free.]

3 thoughts on “Putting the Brakes On Cancer’s Evolution

  1. I survived esophageal cancer in 2003, 1/4 of my stomach and all but 1″ of my esophagus were removed. Was told I had a 30% chance to survive 5 years. Yet here I am.

    I took a daily aspirin for 20 years leading up to the discovery of the cancer. Still do.
    Didn’t seem to help.
    I am available for discussions.

  2. Punctuated Equilibrium!? Neither homology nor analogy; merely conjuring Gould’s ghost. The idea of evolutionary bursts started with Darwin’s 1859 tree diagram (intended to illustrate the principle of (rapid) divergence in sympatry and not the branching itself). With it Darwin illustrated how rapid divergence (periods of stasis punctuated divergence events) could result from competitive interactions between newly formed sister species.
    Gould’s ‘new’ Punctuated Equilibrium was (IMHO) hatched in Gould’s anti-adaptationist political doctrine. Through PE Gould argued (with great imagination) that new biological forms arose through explosive genetic revolutions (an idea now mostly defunct) provoked by founder effects, drift, and physiological readjustments in isolated panmictic populations. Species interactions and catastrophes (and not natural selection) would, in Gould’s view, decide by lottery the nature of extant species. There was little room for adaptive evolution; Darwin, and all thoughts regarding utility, could in due time be forgotten.
    Its reliance on panmixia alone makes PE, as envisioned by Gould, irrelevant to the evolution of cancer.

  3. could the punctuated equilibrium be caused by bursts of transposable elements activation, in other words, temporary disactivation of small RNA pathways?

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