Cancer: Escape route from a “doomed” host?


inline image

A silent pact was made: no eyes to see it, no hands to write it. And yet, one billion years ago, at the dawn of multicellular life, a historic deal was struck governing the cooperation of cells with shared genomes. Implicit in the bargain was the distinction between the cells that would reproduce the organism—the germline—and those of the “vehicle”—the soma. Only one could be propagated, but the advantages of multicellularity for the dispersal of shared genes was enough for the soma to acquiesce—back then, at least. Thus was the soma cursed with mortality; the germline—the very essence of reproduction—would persist, variously mixing its genes with others', sometimes not, in the interminable procession of life.

But the soma remembered the days before its subjugation—that time of outrageous risk, but also freedom—in the form of an ancient survival program passed down from our unicellular ancestors; those who can be claimed as the primordial germline of us all, uninterrupted for 3.7 billion years; mean bacteria, the universal common ancestor, survival machines par excellence. They had witnessed the harshest environmental extremes that any life has survived before or since: blasts of mutagenic ultraviolet combined with a new and potentially deadly gas: oxygen. But not only did they tolerate such insults, they replied with genomic rearrangements, mutations and epigenetic switches. They evolved mechanisms to respond to hostile environments, maximizing their chances by outrageous mutation, unbridled division, dissemination to new niches: survival at any cost. Sacrificing the individual (more often than not consumed by the effects of rampant mutation) secured the procession of life itself. What, indeed, was being propagated at such times of crisis? Genes, or a mere entity capable of reproducing itself? We may well wonder, for the mechanisms that result in unicellular survival have no particular regard for genetic identity: indeed, they can't.

But all the cells of multicellular organisms “behaved themselves” in return for living in the relatively secure environment of a coordinated multicellular whole. Those ancient memories of responding to dire adversity all but disappeared, as cells were lulled into trading off immortality against a stable, but limited, life: one with some degree of replicative potential. However, should the multicellular whole fail, all cells would be committed to a shared, simultaneous death. Any hint of such a malfunction could be taken as an imminent crisis. And so it came to pass that the pact was broken. Something made the normally well-behaved cooperating cells of the organism feel a little uncomfortable with their neighbours and maybe the survival chances of the whole. Perhaps not even their genes would be passed on by their more fortunate germline compatriots. And so they switched on that ancient survival program that disregards genetic identity as the foundation of solidarity. They went it alone, more convinced by their chances of multiplying and breaking free of their “host”. They became cancer cells—ever more genetically dissimilar from their host; enacting a program for survival at any cost.

Maybe this is fanciful, but it incorporates and speculatively develops current unconventional thinking on cancer, most recently from two articles 1, 2 in this issue. In May 2011 BioEssays published a paper arguing for the tissue organization field theory of cancer 3 (on which the above story also draws); several others addressing this, and related new ways of viewing cancer have followed 4, 5, 6, 7. Calls to view proliferation as the default state of cells, and the microenvironment and other epigenetic causes as the trigger for cancer will not disappear; might viewing cancer as a new species bring us yet further? Which ideas await us in 2012?

original image

Andrew Moore