Jake on Pure Pedantry has an interesting post on Evidence for the stem cell theory of cancer development, which I’ve commented on before. Jake’s post is based on a Nature Genetics paper by Martin Widschwendter et al.
I still don’t buy the stem cell theory of cancer. Without a doubt though, some pluripotent cells undergo clonal expansion into neoplastic lesions, and cancer cells share a variety of regulatory characteristics with stem cells. But I think it’s much more accurate to say that cancer cells utilize whatever there is available to get around the roadblocks to proliferation and clonal expansion. Stem cells carry some of these characteristics, and so it makes sense that cancer cells would co-opt the molecular tools which facilitate such characteristics.
Thus, the conclusion that stem cells are the source of neoplasms - though perhaps true some of the time - is incomplete. It’s not a comprehensive description of cancer progression, and does not supplant the other various causes of cancer, including chemical and viral. For later stages, it does not reconcile the roles of chromosomal damage, elevated tyrosine kinase signaling, or why p53 and other vital tumor suppressors may be lost, in many cancers.
But most critically in this topic, Widschwendter and colleagues base their support of this theory on the correlation of a set of epigenetic markers, not a cause and effect study. They simply do not address whether tumor cells could have acquired the DNA methylation signature that they examine without originating from stem cells, which I think is still a perfectly reasonable possibility.
Methinks the evidence for this theory is still fleeting.
