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Thursday, October 18, 2007

An interview with Tyler Jacks on the new David H. Koch Institute for Integrative Cancer Research


Tyler Jacks, who will direct the new David H. Koch Institute for Integrative Cancer Research, is currently the director of MIT's Center for Cancer Research. In this interview with News Office writer Anne Trafton, he discusses his vision for the new center and the cancer research that will take place there.


There are many research institutes around the world working on cancer--how will the MIT approach be unique?


The new center will be different both from what it is today and from other cancer centers, in that it brings together scientists and engineers focused on cancer. The real power is in having cancer biologists that are expert in the disease, working on trying to understand the disease at a molecular level, interacting closely with engineering faculty with an interest in solving cancer-related problems. There are other NCI-designated basic science cancer centers besides our own, but none with the composition of interdisciplinary investigators that the Koch Institute will have.


What are some example areas where this collaboration between biologists and engineers will be beneficial?


One example is an area that we call systems oriented cancer biology, where we are trying to understand the complex nature of cancer and the kinds of growth control networks that control the behavior of cancer cells. Here we're using methods from engineering, mostly with biological engineering faculty collaborators, to develop mathematical and computational models to explain why cancer cells proliferate abnormally, fail to die when they should or how they respond to therapy.


Another example is in the area of nanotechnology, where we are hoping to develop a new generation of anticancer agents which are more powerful because they can selectively target cancer cells, as opposed to normal cells. That will be enhanced still further in the future by taking advantage of new information from biological studies regarding how to shut off any gene of interest. This takes advantage of a process called RNAi, which has only been discovered in the past 10 years or so. Many members of the science side of the cancer center are actively working on this area with the goal of developing new therapeutic approaches that will really change the range of targets that we can go after. These kinds of collaborations highlight the importance of having scientists who are knowledgeable about the disease and knowledgeable about biology working with engineers who want to develop new tools, new materials, new devices, that can be used to better diagnose or better control the disease.


How will the center's physical design help facilitate collaborations between the researchers in the building?


The way we are designing the building is to have each floor have both biologists and engineers. The decision as to which floor would have which engineers and which scientists was determined in part by areas of shared interest among those faculty. We tried to create groupings that would help maximize the likelihood that the laboratories would end up interacting, and those on a given floor will have an even greater chance for interaction. We obviously don't want to limit that to researchers on a given floor, and indeed, we expect the interactions to take place throughout the building. One of purposes of having a building housing all of us is to maximize the opportunities for direct interaction, whether it's formalized, in group meetings and so forth, or informal. By bumping into somebody on the way to the copy machine or in the tea room, you might initiate a new line of investigation or help shed light on an old problem by bringing a new perspective.


Which faculty members will be involved in the groupings?


Let me mention three specific examples, which are just a few of the many interactions that we hope to foster in the new institute. Phil Sharp and Sangeeta Bhatia will be together on the forth floor. They are jointly interested (along with Bob Langer and others) on developing nanotechnology applications for cancer. On the third floor, Forest White will be paired with Michael Yaffe, Richard Hynes and Frank Gertler. They will interact closely on the systems-oriented cancer biology project. Another example is the pairing of Dane Wittrup and Darrel Irvine with Jianzhu Chen. All of these investigators are interested in deploying the immune systems to combat cancer, using a range of methods from protein engineering to improved vaccine strategies to developing more potent cytotoxic T cells.


What major advances in cancer research do you foresee in the next 10 to 20 years?


I think in the next 10 to 20 years several important things will happen. First, our knowledge of relevant cancer pathways will become even more complete, and the pace of that process will accelerate dramatically. That will provide us with what we're calling a complete wiring diagram of a cancer cell. That is important because once you understand the full detail of the problem, it allows you to design your best means of attack. The right approach might not be obvious until you have a very complete picture of how things are wired. Such information is not merely important to scientific advance but rather is necessary to allow us to develop even more potent and more effective therapies. Moreover these insights allow us to intervene earlier and earlier in the disease; when caught early cancer is almost always manageable.


Another area is in nanotechnology. We need to create a new generation of anticancer drugs that goes beyond both the conventional agents, which have been around for 50 years or more, and also goes beyond the new class of molecularly targeted anticancer agents. In the near term we imagine the marriage of nanotechnology with RNAi, with which our ability to control cancer cells will be much more effective. To get there, we're going to need to solve some problems, including, importantly, delivery--how to get the RNAi molecule into every cancer cell with very high efficiency. We're going to be relying on our engineering colleagues to solve this problem.


Also, I'm quite convinced that the immune system can be used to control cancer, either in a cancer prevention context or in cancer treatment. Although investigators have tried to create cancer vaccines or use cells in the immune system to fight cancer for some time, this approach has not been very successful to date. It's my opinion that we have to invest more in the basic science to understand the interactions between the immune system and cancer more fully. With our engineering colleagues, we need to design out ways to engineer the immune system to fight cancers more effectively.


The last example I'll mention is the development of devices that will monitor the state of an individual's disease. Let's imagine a cancer patient who is diagnosed and treated, perhaps with surgery or with chemotherapy. The cancer goes into remission, and then it's important to track whether the tumor remains in remission or is undergoing relapse. The way that's done today is with periodic checkups. You go to the doctor and undergo some screening tests. If the test comes back positive the cancer has returned. The problem is that if the test comes back positive, the cancer might have returned in a very aggressive stage or may have returned weeks or months before. So what we're trying to do is develop devices that can be implanted in the body and monitor continuously the presence of tumor cells. The patient would know not year to year but literally minute by minute what's the state of their disease. That information could be transmitted out of the body and directly to their oncologist, so that as soon as a problem became apparent, the treatment could begin. In the most sophisticated incarnation of that idea, the oncologist could actually be cut out of the picture entirely. That is, the device could be so smart that once the cancer cells were detected, a therapeutic agent could be released which could eliminate those cells even before clinical symptoms were apparent. We're not there yet, but you'd be surprised at how many of the component parts of what I just described are in place.



A version of this article appeared in MIT Tech Talk on October 17, 2007 (download PDF).




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