Ongoing and Future Directions of NOB
The general failure of molecularly targeted agents to impact significantly on the clinical outcome of patients with cancer in general and gliomas specifically, raises the possibility that the signaling apparatus of the cancer cell represents a non-linear, democratic network constituting a robust, highly intertwined matrix of interconnected signaling modules such that the inhibition of any one (or combination of) aberrant proximal signaling pathway(s) in that network is unlikely to reverse the stability of the network.
We have entered into an integrative research effort devoted to the identification of points of signaling intersection, or nodes, within the cancer cell network that are central and thus required for maintenance of the cellular state. This approach requires the use of a model system that is as molecularly and genetically similar to human gliomas as possible. We believe that this lofty goal is increasingly within our reach given our growing expertise to isolate and work with tumor stem cells and to the advent of high throughput genomic technologies and the computation and bioinformatic methodologies to analyze the resultant data.
Thus, for the foreseeable future, our research will be based on the working hypothesis that the integration of glioma genomics, cancer stem cell biology, normal neural stem cell/developmental biology, clinical/imaging data with computational biology will significantly advance our understanding of gliomas. Through this approach, we firmly believe that a series of new molecular pathways and networks related to developmental and stem cell biology will be identified that are not currently considered within the realm of commonly accepted cancer targets. Through the principles learned in this integrative approach and through the thoughtful translation of these principles into meaningful clinical/translational research, improved therapeutics will be realized.
To make our efforts a reality, the Neuro-Oncology Branch (NOB) has made a significant effort over the last four years to build the stem cell, neurobiology, computational biology, and clinical expertise within NOB to position us to successfully move toward this highly ambitious integrative research model.