Sunday, September 21, 2008

Cancer: a microcosm of evolution

With the imminent arrival of a next-generation sequencing capability at the University of Birmingham (sequences 100x faster and cheaper than before), many new previously undreamt of research opportunities are opening up. I spent last Friday morning rushing around editing, printing and delivering a proposal for a medical school studentship with the head of cancer studies to use deep sequencing to follow the evolution of a cancer gene in chronic lymphocytic leukaemia. Such deep sequencing in cancer, whether of single genes or whole cancers, is now all the rage. 

What has cancer got to do with evolution? Well, lots! In recent years, it has become clear that Darwin’s theory of evolution by natural selection applies at the cellular level, with natural selection clearly driving the evolution of cancer cells. In a cellular struggle for existence, cancer cells compete for space and resources, evade predation by the immune system and evolve to disperse and colonise new organs. In addition, cancer cells evolve in response to treatment, often becoming resistant to anti-cancer drugs. Here are a couple of recent references:

  • Merlo LM, et al. (2006) Cancer as an evolutionary and ecological process. Nat Rev Cancer. 6(12):924-35. 
  • Goymer P. (2008) Natural selection: The evolution of cancer. Nature. 454(7208):1046-8. 

And our view of cancer grows ever more sophisticated. Although for many years, it has been accepted that cancer is usually a clonal phenomenon, i.e. any given cancer arises from a single cell, it is now clear that the cancer cell population in fact represents a diverse and dynamic cellular ecosystem, with many sub-clones bearing adaptive (driver) mutations and neutral (passenger) mutations emerging, persisting and/or undergoing extinction

And as proof that roaming the blogosphere can take you places you don't usually stumble upon in the peer-reviewed literature, I recently came across these two blog postings, which discuss the terrifying idea of transmissible cancers:

Fortunately, evolutionary theory does not just provide us with better explanations of cancer, but also provides new cures--a few months ago, I heard Cambridge molecular biologist Greg Winter describe how he had used a Darwinian approach to select for modified antibodies active against cancer.

1 comment:

Rafe Furst said...

Mark, nice post.

Just FYI, I've been tracking somatic evolution on my blog as well and have highlighted some of the same recent advances. Here's a summary post. Other evolution-related posts here.

You might want to add check out Basanta's Cancerevo blog to your blogroll as it's entirely on topic.

Also, the link to the Greg Winter reference is broken...