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Defining Cancer, Gene By Gene (continued)

Q: The trick is always to stay two steps ahead?
A: That's what we're trying to do. And the key is that Dr. Richard Klausner facilitated organization of CGAP in such a way that we can rapidly respond to new opportunities and CGAP can meet the needs of the cancer research community.

Q: Four years later, how do you feel about the success of CGAP?
A: I still believe firmly in the vision that we put forward four years ago. But, we're not going to be satisfied until we reach our ultimate goal: improved patient outcome. That is what this is all about. So, CGAP is not just a success because we built catalogues. It's really being able to build those links that improve the lives of patients. I'm quite encouraged that not only have the databases been created, but the databases have been, in fact, useful. I point to the early results from the cDNA microarray data. Again, there was this vision that we could segment cancers based on their unique molecular profiles, that we would learn that some people respond better to a particular therapy because they actually have a different cancer than another segment of the population. I think that this is clearly turning out to be the case. I think that vision has held up remarkably well and has been well demonstrated within a four-year time span. Already, we see the community moving toward expanding these data sets, of really moving this into the clinical arena, of developing diagnostic tests that would be based on the molecular form of cancer, not just on microscopic analysis. Most importantly, we are now starting to benefit in the clinic from many years of research toward identifying molecular targets whose perturbation can result in exciting new intervention strategies. While you can never be fully satisfied in science, I think that the vision that was put forward for CGAP holds up very well today. I still think that it provides a very good framework for moving forward over the next few years.

Q: So, the real rewards are really yet to come?
A: I think that many rewards will come over the next decade, and we will see the translation of CGAP data into practical components of cancer care. That is really the key for me. The end goal is not to do the transcriptome, or to know what's expressed in the prostate. It is really turning it into practical applications, and that prospect is what I find most encouraging.

Q: What about the future of CGAP?
A: I think that we will begin to see practical products coming from CGAP, the process of discovery, for many years to come. While our gene index project is now in a mature stage, we can't just be satisfied by cataloguing genes. We have to continually think of new approaches that will give us the most useful molecular information about cells that are likely to turn cancerous, and how to best intervene for successful patient outcome. At a certain level, I think that as our cataloguing of genes becomes complete, it leads to more of a quest for knowledge. Cancers are comprised of a very heterogeneous group of cells; therefore we'd like to understand not only the overall molecular features of a tumor, but also at the cellular level, which key cells in cancer development can be best targeted. In addition, we want to be able to look in vivo at gene expression. The current CGAP datasets come from tumors that have been removed from patients. New technological advances will eventually allow us to have catalogues of genes based on in vivo monitoring, which will give us the best picture of what is happening directly in the patient. We will continue to build on the efforts of the CGAP Genetic Annotation Initiative. The GAI is assembling information on the diversity of the genome in the human population, the molecular changes of the genome as cancer progresses, and how those differences are manifested in gene expression. The same is true with the CGAP Cancer Chromosome Anatomy Project. This project presents an exciting opportunity to link gene information with changes at the chromosomal level. This brings me back to the bioinformatics. I think that the seamless interface of all of these data sets is certainly a realizable goal for CGAP. There will be many creative strategies for preventing and intervening in cancer, and we'd like to assure that the platform for these efforts—databases of all of the molecular changes associated with cancer—are available to the entire research community. So, I think that pushing the envelope is going to be a continuing CGAP theme. There is an ongoing interface of the clinical and basic research communities that will help to define the CGAP mission. I don't think that we could ever look at completion as such, but rather completion of a particular approach and saying, "What new opportunities arise from the current advances by CGAP and from biomedical research in general?"