[gdpawel]

One of the hallmarks of cancer is the complex interaction of genes, networks, and cells in order to initiate and maintain a cancerous state. This inherent complexity constantly challenges our ability to develop effective and specific treatments. A systems biology approach towards the understanding and treatment of cancer examines the many components of the disease simultaneously.

Genes do not operate alone within the cell but in an intricate network of interactions. The cell is a system, an integrated, intereacting network of genes, proteins and other cellular constituents that produce functions. One needs to analyze the systems' response to drug treatments, not just one or a few targets (pathways/mechanisms).

Sequencing the genome of cancer cells is explicitly based upon the assumption that the pathways - network of genes - of tumor cells can be known in sufficient detail to control cancer. Each cancer cell can be different and the cancer cells that are present change and evolve with time.

There are many pathways/mechanisms to the altered cellular (forest) function, hence all the different "trees" which correlate in different situations. Improvement can be made by measuring what happens at the end (the effects on the forest), rather than the status of the indivudal trees.

Dealing with genome-scale data in this context requires of its functional profiling, but this step must be taken within a systems biology framework, in which the collective properties of groups of genes are considered.

The importance of mechanistic work around targeted therapy as a starting point should be downplayed in favor of a systems biology approach were compounds are first screened in cell-based assays, with mechanistic understanding of the target coming after validation of its impact on the biology of the cancer cells.

What would be more beneficial is to measure the net effect of all processes within the cancer (cell-based functional profiling), acting with and against each other in real-time, and test living (fresh) cells actually exposed to drugs and drug combinations of interest. The key to understanding the genome is understanding how cells work. How is the cell being killed regardless of the mechanism.

Like the various influences on a flower seed that cause one blossom to turn out differently from another, there are biological processes in the body that affect the development of cancer in each patient and determine how that patient's cancer cells will uniquely react to treatment.

Source: Cell Function Analysis