Do you think (cancer) medicine is modern? The need for a new cancerparadigm
1Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Around the millennium three decades of successful research on cancers were concluded in the most cited review on cancer ever “Hallmarks of Cancer” (Hanahan and Weinberg, Cell, 2000). It marked the end of an era when oncogenes and suppressorgenes were discovered en masse, and when tumor progression at the level of cell and tissue pathology could be linked with molecular steps like that by Bert Vogelstein of colon cancer progression (“The Vogelgram”). Cancer was a disease of cells and depended on mutations of some ten genes. Tumor progression was an evolutionary, Darwinistic process at the tumor cell population level. This seemed so transparent and logically sound that the scientific community at large believed it had understood cancer.
During the same time the understanding of cell and tissue biology made quantum leaps in new directions. The conclusions are: we do not really understand cancer biology, and cancer is a very complex disease reflected by the enormous complexity of its “host” – the cell. Major findings have been: epigenetic deregulation, cancer tissues are highly heterogenous, microRNAs as a new set of regulatory genes, low level chronic inflammation is a key component in early carcinogenesis, there are rather several thousand mutations in cancer, and cancer cells usually switch metabolism from oxidative glycolysis to fermentation (the Warburg effect). How can we comprehend all these significant findings in our understanding of cancer biology?
In medicine today we are challenged by short-comings of simple linear models of cause-effects, like that of the presiding cancer model, while much suggests that a living system is even better described in terms of a complex adaptive system. We are in great need of new tools to study complex systems. We are exploring experimentally a model for this, the cell attractor model.
If successfully pursued, cancer as a complex adaptive system will certainly affect biomarker discovery and provide new concepts of treatment.
Keywords: Biochemistry, Cancer, Genomics