This month's issue of Future Oncology has a well-written editorial from Dr. John McDonald from Georgia Tech regarding systems biology in cancer research. This is a free download and I highly recommend it as a nice overview contrasting the traditional "reductionist" approach to cancer cell biology research versus the emerging application of a systems biology approach.
First, it is appreciated that the traditional approach has grudgingly yielded some valuable insight into cancer cell biology which has led to the development of "rationally designed" targeted therapies. But while many of these therapies have had some initial impact for patients enrolled in clinical trials (and even some dramatic responses), I think it is fair to say that they also have not radically shifted overall survival or long-term outlook of the most common lethal cancers.
However, we are beginning to realize the potential for combining high-throughput molecular technologies with computational strategies and capabilities for combining multidimensional datasets to find inferred network relationships. Dr. McDonald refers to this as the "top-down" approach. He contrasts this with the traditional reductionist "bottom-up" approach which links human oncogenes or tumor suppressor genes with known interacting genes previously characterized in experimental models using cancer cell lines or animal models to identify signaling pathways implicated with cancer. He stresses that these approaches are by no means mutally exclusive but indeed are complementary.
The systems approach starts with establishing a list of component parts. Using new technologies, we can now speak of the genome, transcriptome, proteome, metabolome, etc. The revolutionary step is using sophisticated computer models to detemine how these various components interact and which of these interactions are relevant for cancer initiation and progression and which represent potential druggable targets.
Again, this is a nice appetizer for additional reading on this exciting area!
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