Cancer development has long been recognised as a clonal (single cell origin) disease, akin to a Darwinian process of genetic (mutational) diversification and natural selection within the tissue ‘habitats’ of the body.
Therapeutic intervention represents the ultimate selective pressure and frequently begets the selection of rare variants of cancer cells that can resist the drugs used. But details of the dynamics of this process have been difficult to ascertain and potentially profound clinical implications largely ignored.
Leukaemias offer a tractable approach to this problem and the study by Anderson K et al (Nature, 2011; 469: 356-361) represents a major advance in our understanding. By scrutinising hundreds of single cells from childhood acute lymphoblastic leukaemia for their mutational complexity, the authors were able to reveal the sub-clonal architecture of cancer and infer its evolutionary history.
The emergent picture is remarkably reminiscent of Charles Darwin’s iconic 1837 drawing of an evolutionary tree illustrating evolution by descent from a common precursor (see picture). In a collaboration with Professor Tariq Enver’s Leukaemia & Lymphoma Research-funded team, the authors went further to show that the sub-clonal branching structure was maintained by so-called leukaemic stem cells that were themselves genetically diverse, though descended from a common founder cell.
These novel observations strongly endorse the evolutionary paradigm for cancer biology and help explain the difficulty in eradicating advanced disease: evolutionary diversity of the driving cancer stem cells provides escape routes from therapy. Clearly, the much heralded targeted therapy (or ‘personalised medicine’) is unlikely to succeed unless all sub-clones are eradicated or controlled. Cancer needs a Darwinian bypass.
Several very recent papers (February/March 2012) have replicated the above findings on clonal architecture, for other leukaemia types and for ‘solid’ cancer.
For a recent and comprehensive review of the evolutionary biology of cancer and its clinical implications, see: Greaves M & Maley CC. Clonal evolution in cancer. Nature, 2012; 481: 306-313.
Professor Mel Greaves of the Institute of Cancer Research is a world-renowned authority on childhood leukaemia. Leukaemia & Lymphoma Research have funded his groundbreaking research since the 1970s.