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Dr. Todd Golub is director of the Broad Institute of Harvard and MIT. He believes that his team of researchers, which also includes biologists from the Dana-Farber Cancer Institute and oncologists at Harvard Medical School, may be hot on the trail of the next promising new drug treatment. In this exclusive interview with the Prostate Cancer Foundation, he explains what led to his groundbreaking new study and how it could revolutionize the way that prostate cancer is treated.
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PCF: You've received PCF funding to research ways that might stop something called “translocation” of chromosomes. Would you describe in layman's terms what that means?
Dr. Golub: Yes. We know that all cancers are caused by mutations of some kind in the genome. In this case, two different chromosomes break in the middle and fuse to each other to create a new gene. We used to think this process only occurred in leukemia, but a discovery a couple of years ago demonstrated that it occurs in prostate cancer, and it occurs really frequently. This was one of the most significant discoveries in prostate cancer in recent times, because it pinpointed the genes that are likely to be involved in causing prostate cancer. It also suggested that this is where we should focus the effort to discover new therapeutic approaches.
PCF: That was an important step of progress. But it came with a challenge, didn’t it?
Dr. Golub: The challenge was that the gene disrupted by this translocation turned out to be one that manufactures proteins that turn other genes on and off. The details don't really matter, except that the traditional approach to finding new drugs for use against cancer does not work with this kind of gene. The genetics of prostate cancer were screaming out, "Here is what's important." But they weren't receiving much attention.
PCF: How did you and your colleagues solve the problem?
Dr. Golub: We developed what I think are some innovative experimental methods for thinking about the drug discovery process. The idea is that we can use information about which genes in the prostate cancer cell are turned on and off when an abnormal protein is active to determine the level of activity of this abnormal protein. Once we have this information, we can screen a large collection of chemical compounds for their ability to turn off the process. We're also using new approaches to screening that enable us to look at the interaction between chemical compounds and the translocated genes we are targeting in a much more miniaturized way. And we're using a new technique that will allow us to identify parts of the genome that are critical to the survival of prostate cancer cells.
PCF: Why are you so excited that this research is taking place now?
Dr. Golub: This project represents a convergence of a lot of exciting things. One is the discovery of the translocation that we've been talking about. The second is the maturing of new technology. For the first time ever, you can take on a project of this complexity. You could have had the idea five years ago, but you couldn’t have done anything about it.
PCF: Is there a cure for prostate cancer on the horizon?
Dr. Golub: I think there will be a cure for prostate cancer. I think this is a solvable problem. It's a hard problem, and it's going to take time to work out. But the more I learn about this disease, the more optimistic I am that it is a solvable problem and that the solution is going to come from these types of PCF-funded initiatives that are bold and ambitious and multi-disciplinary.
PCF: In your opinion, what is the greatest obstacle to finding a cure?
Dr. Golub: Well, the biology of prostate cancer is very complex, and we need to better understand that biology. But I also think it goes without saying that the current state of NIH funding for prostate cancer is inadequate. This makes it all the more important that groups like the Prostate Cancer Foundation fill the gap. Otherwise there is a very high probability that tremendous potential will not be acted on because of lack of funding.
PCF: How important has PCF funding been to your research?
Dr. Golub: This project wouldn’t be happening without it. We had the idea to do this kind of research previously, but it was on the shelf until PCF found a way to fund it. It's critical, yet it is the sort of high-risk, innovative approach that is not easily funded through other mechanisms such as the NIH. PCF was visionary enough to invest in this unconventional but very powerful approach.
PCF: Is there anything you would like to say to PCF’s donors to help them understand the significance of what they are involved with?
Dr. Golub: I think they need to understand that this is an unprecedented moment in the history of cancer research. The problem isn't solved, but we're starting to understand for the first time how to solve it. We have new tools, new insights and more powerful technologies than we have ever had before. Yet funding through the usual government sources has not risen to the challenge, so it’s PCF donors who are making this possible.
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