Stand Up To Cancer

Thank you to everyone from our community who submitted questions for the SU2C scientists. We received many fantastic ideas from you, and were able to pose several of the questions to the scientists during the American Association for Cancer Research 101st Annual Meeting 2010, which was held in Washington, D.C., April 17-21.

Bedonna, a member of the Stand Up To Cancer production and web teams, blogged about what she learned at the Annual Meeting; if you haven't read her blog entry yet, be sure to check it out.

Responding to our call for questions, SU2C community members Kelli, Lon and V. asked about the "little guys" -- rarer cancers that don't receive as much media attention and research funding, which are sometimes called "orphan cancers." We asked the SU2C scientists about how their research could impact these diseases. As you may know, the concept of treating cancers based on their organ of origin is rapidly falling by the wayside as scientists discover genetic commonalities between cancers once thought of as different.

Collaboration within and between the Dream Teams helps scientists find these commonalities much faster. Lewis C. Cantley, Ph.D., director of the cancer center and chief of the division of signal transduction at Beth Israel Deaconess Medical Center, professor of systems biology at Harvard Medical School, Boston, and leader of SU2C's "Targeting the PI3K Pathway in Women's Cancers" Dream Team, noted that "there is really no mechanism at the National Institutes of Health, National Cancer Institute or Department of Defense that does what the Dream Team concept does." Cantley went on, "Shouldn't we be targeting cancers based on the molecular events that take place and distribute our trials based on that, rather than the tissue of origin for the cancer? That's absolutely where it's going to go. We now know that there's more similarity, for example, between colorectal cancer and endometrial cancer than there is between endometrial and ovarian, for example. And there are common events between pancreatic, endometrial or ovarian. It's important that our Dream Team groups get together and compare information. We're paying very close attention to each other's research and will be very much connected between the groups."

During an unprecedented roundtable discussion between Innovative Research Grant (IRG) recipients, Elizabeth R. Lawlor, M.D., Ph.D., an IRG recipient who is an assistant professor in the department of pediatrics and pathology at the University of Michigan, Ann Arbor, added, "Most tumors in pediatric oncology can be considered orphan diseases. So, if you study a tumor in isolation, even if you identify a great drugable target, you're never going to find a company that's willing to take that drug into development, because they're unlikely to be able to recoup their investment. For all orphan diseases or rare tumors, it's critical that we work to try to identify pathways and targets that are common among different tumors. That's the only way we're ever going to promote the development of novel agents that will have any realistic chance of getting to the clinic through the pharmaceutical companies."

SU2C community member Melanie asked, "How close are we to seeing drugs that can kill cancerous stem cells?" This topic was addressed by Dr. Lawlor, whose work on Ewing sarcoma has led to the investigation of stem cells research. During the roundtable session, she said, "It's become clear that Ewing sarcoma probably comes from a stem cell. Doing studies on normal stem cells to understand how they would develop normally and how the normal development is hijacked to form a sarcoma is difficult, but essential. If we are going to effectively target cancer stem cells without destroying normal stem cells in the process, then we need to understand what the difference between the two are and then exploit these differences. We've developed an innovative technique to make neural crest stem cells in the lab using embryonic stem cells. We are studying these normal stem cells before and after introduction of the genetic mutation that causes initiation of Ewing sarcoma. The ultimate goal is to be able to reverse the cancer process, or stop it from progressing further, without adversely affecting the health of the normal stem cells."

SU2C community member Damon asked about the toxicity of chemotherapy and finding better ways to target treatments to specific patients. This is an area of focus for many of our scientists, and several of them addressed this issue. Matthew Levy, Ph.D., an SU2C IRG recipient who is an assistant professor in the department of biochemistry at Albert Einstein College of Medicine of Yeshiva University, said, "One of the challenges with treating cancers is that the drugs that are used are toxic to all cells in many cases. There's a big drive to get drugs to the cells that are sick and avoid the healthy cells." Dr. Levy's work focuses on larger molecules called macromolecules that target drugs to the cancer cells. One class of macromolecules that he works with is called aptamers, which are composed of nucleic acids that function like antibodies. "We hope to use and adapt aptamers for delivering drugs to cancer cells. We also want to develop new methods to target cancer cells; we are trying to take the methodology that we used to develop these molecules into the animal to specifically target tumors. By combining those molecules with the technologies that we develop to deliver drugs, we hope to be able to target cancer cells and mitigate side effects," he said.

Craig B. Thompson, M.D., director of the Abramson Cancer Center at the University of Pennsylvania and co-leader of SU2C's "Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer" Dream Team, picked up the thread of this discussion, noting that targeting treatment "is absolutely the critical issue going forward." He went on, "The problem is we can't go re-biopsying patients any time we want. One hope with the Dream Team from MIT is that can we use circulating tumor cells to test new drugs for tumor-specific effects. I think the other hope is functional imaging in Cantley's group ['Targeting the PI3K Pathway in Women's Cancers']. That can be done repetitively in people." Dr. Thompson also discussed leiomyosarcoma, a rare, aggressive form of sarcoma that was referenced by SU2C community member Richard, whose wife has been in clinical trials for the disease for six years. "Tomorrow morning there'll be 100 uterine leiomyosarcomas delivered to my lab to test the metabolic strategies that have evolved out of our team's work. We are going to be investigating that because it's where the process leads us next," Dr. Thompson said.

Charles M. Roberts, M.D., Ph.D., an SU2C IRG recipient who is an assistant professor in the department of pediatrics at Harvard Medical School and an assistant professor of pediatric oncology at the Dana-Farber Cancer Institute, Boston, offered a differing perspective on the issue of biopsying metastases. "There is the possibility that if we do biopsy these unknown metastases, we may be able to identify mutations that we can do something about," he said. "What we then learn is what's going wrong in these metastases that are leading them to be there. The amount of scientific knowledge that can be obtained in this way is immense."

Finally, SU2C community member Don wrote, "We always need a reason to keep pushing, trying and never give up." Words spoken by Dr. Cantley during a closed session offer a great explanation of what makes SU2C's model so unique, and give us a reason to keep working for collaborative, translational research. He said: "We're now seeing oncologists, surgeons and pathologists talking to basic scientists. We're all speaking the same language. Even 10 years ago, it was rare for a basic scientist to have a discussion with an oncologist about a clinical trial. We didn't really understand enough about the basic science of the cancer for the basic scientist to have anything to say to the oncologist that would help them improve the trial. And that's now changed. We understand cancer at a molecular level in a way that we never have before, even more than we understood it four or five years ago. This creates a very exciting scenario where we can collaborate and design trials based on molecular events that are happening in individual patients."

Nobel Laureate and SU2C Scientific Advisory Committee Chairperson Phillip A. Sharp, Ph.D., who is an institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, said, "This is going to have a very important impact, not only on the people in this room, but people outside this room who are planning national programs and thinking about the future of cancer research. We're currently at an even bigger experiment than what we started off to do, and I'm very pleased to be part of this effort."