Abstract:
Until the last century, infectious diseases were the leading cause of human mortality. Therefore, our current medical reasoning is profoundly influenced by views that originated from medical microbiology. The notion that cancer growth is sustained by a sub-population of particular cells, the cancer stem cells, is highly reminiscent of the germ theory of disease as exemplified by Koch’s postulates in the XIXth century. However, accumulating data underscore the importance of cell-cell interactions and tumor environment. Hence it is essential to critically review the basic tenets of the cancer stem cell concept on the light of their relationships with Koch’s postulates. Shifting the pathogenic element from a special cellular entity (cancer stem cell or microorganism) to a “pathogenic field” could be critical for curing both cancer and drug-resistant infectious diseases.Excerpt from the "Concluding remarks" in the full text (which isn't freely-accessible):
Indeed, the reductionist and oversimplified cancer stem cell paradigm which originates from the implicit application of Koch’s postulates should progressively evolve towards a “tumorigenic field” concept, just as the “one gene _ one protein _ one phenotype” paradigm has evolved towards epistasis ...
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Well-chosen "reductionist and oversimplified" initial approaches to complex problems can yield fruitful results. Perhaps this recent report provides an example?
ReplyDeleteSee: Species-Specific Transcription in Mice Carrying Human Chromosome 21 by Michael D. Wilson and 8 co-authors, Science 2008(Oct 17); 322(5900): 434-8. PubMed Abstract:
Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor-binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.