How many mutations does it take?

For some time before we had the benefit of cancer genomics, it was generally believed that for a cancer to disseminate and become potentially lethal, it would have had to accrue several mutations that, collectively, would provide a kind of ‘full house’ for malignancy.

It was further assumed that, in the absence of rampant genetic instability, the critical set of mutations would arise one at a time and that it would, therefore, take time to assemble a ‘full house’ set. The linear relationship of cancer incidence to age (in log-log plots) was taken to indicate that four to six rate-limiting mutational events might be involved 1,2. However this inference rested on some questionable biological assumptions 3. Continue reading

Background: Darwin’s branching tree of evolutionary phylogeny

Transmutation notebook B

Charles Darwin’s Transmutation notebook B, 1837

Since the turn of this century, cancer genomics has strongly endorsed the Darwinian view of cancer biology 1,2. Interrogation of the genomes of single cancer cells and multi-regional small biopsies of tumours have allowed us to construct evolutionary histories, or phylogenies, of cancer clones – revealing genetic and cellular architectures very reminiscent of Darwin’s iconic drawing of evolution or speciation 2. Continue reading

Background: What has evolution got to do with cancer?

Charles Darwin by Ernest Edwards albumen print, 1865-1866 NPG x1500 © National Portrait Gallery, London

Charles Darwin
by Ernest Edwards
albumen print, 1865-1866
NPG x1500
© National Portrait Gallery, London

‘No man, even under torture, can say exactly what a tumour is.’
J. Ewing, 1916

What exactly is cancer? Can we capture its biological essence in a few words or a phrase? For the ancient Greeks, it was a manifestation of black bile, or constitutional melancholy. The common understanding today is that it reflects renegade, mutant cells proliferating out of control, with a potentially lethal consequence: a territorial hijack of essential, normal tissue functions. Continue reading

Time for a new perspective on cancer?

Charles Darwin by Julia Margaret Cameron albumen print, 1868 NPG P8 © National Portrait Gallery, London

Charles Darwin
by Julia Margaret Cameron, albumen print, 1868, NPG P8
© National Portrait Gallery, London

Evolution by natural selection is the foundation law of biology. So we shouldn’t be surprised that it has great relevance to cancer.

‘Nothing in biology makes sense except in the light of evolution’
Theodosius Dobzhansky, 1973

Almost 40 years ago, Peter Nowell first championed the idea that cancer is, fundamentally, a process of somatic cell evolution 1. Since then, the concept has been validated and elaborated, such that the striking parallels with Darwinian speciation by natural selection in ecosystems have been highlighted on many occasions 2,3,4. Continue reading