The focus of the 28-person team scattered across five institutions is to better understand the metabolic changes that characterize pancreatic cells. It’s a collaborative exercise that starts when surgeon Jeffrey Drebin of the University of Pennsylvania removes a tumor from a diseased pancreas. He carries it from the operating room to a lab, where it is flash-frozen for preservation. Penn’s lab sends a specimen to the Salk Institute’s Gene Expression Laboratory, where researcher Geoffrey Wahl and colleagues analyze the state of stellate, or star-shaped, cells that are usually involved in tissue repair but may play a role in cancer as well. Another sample goes to Princeton, to the lab of Joshua Rabinowitz, who analyzes amino acids, sugar and up to 300 metabolites. Team members at Johns Hopkins and Translational Genomics analyze the genome sequence.
One of the theories emerging from this group is that pancreatic cancer cells communicate with stellate cells that also show up around the tumor and conspire to ward off immune responses and build resistance to chemotherapies. The tumor cells seem to leech glutamine and other amino acids from the rest of the body to feed the tumor — one reason people with pancreatic cancer lose so much weight. Prevent the hijacking of glutamine and other amino acids and perhaps the tumor starves. The team has also discovered that vitamin D can help stop the scarring around the cancer, giving the immune system or chemotherapies better access to cancer cells.
Within two years, they had modeled, evaluated and tested an albumen-containing drug that shows promise in increasing the efficacy of treatments. They enrolled 861 patients in a Phase III clinical trial of a treatment for advanced pancreatic cancer that adds the chemotherapy drug Abraxane, and the results have been encouraging: the combination stabilized the disease in 48% of the patients, doubling the two-year survival rate — to 9%, which tells you how diabolically difficult the cancer remains. Remarkably, though, a few patients have had a complete remission. “This combination is a new standard,” says Von Hoff, “and most important, one that you could build on. This kind of broke the logjam.”
Something similar is happening at MD Anderson, where physicians and researchers who may have worked separately on breast cancer and ovarian cancer, for instance, are joining forces because the genetic markers are telling them the cancers are related. Exploiting connections, says Dr. John Heymach, an oncologist at MD Anderson who is part of an SU2C dream team focused on circulating tumor cells, “is where team science becomes important. It’s a pattern-recognition exercise. We are going to accumulate data and expertise. We are going to profile all these different mutations.”
Bree Sandlin is among the thousands of patients at MD Anderson rooting for the Moon Shots program. She’s a 37-year-old marketing executive for Shell who has twin boys and triple-negative breast cancer — so named because receptors for estrogen, progesterone and a growth factor known as HER-2/neu are missing. This makes treatment difficult, since those are targets for hormone and drug therapies. She’s in a clinical trial that is testing the effectiveness of eribulin, a cancer drug typically used in metastatic breast cancer, as an adjuvant — an immune-system kick-starter. So far, it’s working well. “That approach to research is just very different than how they used to approach it in the past,” she says. “It can’t help but give me hope.”
More hope for other potential patients is coming from the new platforms MD Anderson has added around prevention and early detection. If patients like Sandlin are genetically predisposed to breast cancer, what about other women in the family? If they are offered testing for the same biomarkers, the doctors could head off big trouble by catching any cancer early. Likewise, there are 94 million ex-smokers in the U.S., meaning they have elevated cancer risk. Subjecting each of them to an annual CT scan would catch early-stage lung cancers and reduce mortality from the disease by perhaps 20%. Given that there are 175,000 new lung cancers diagnosed every year, that’s a lot of lives. But getting all those people into a CT machine is neither practical nor even possible. Instead, MD Anderson is developing a simple blood test for a protein marker that could, when used in combination with diagnostic imaging and risk models, detect lung cancer earlier than it is typically found.
Team science isn’t appropriate for every aspect of cancer research. Nor is it issue-free. One question up for grabs: How long should a team be together? SU2C’s initial funding is for three years, although some teams have secured money for additional years. The pancreatic team, for instance, just received two grants of $2 million each from the Lustgarten Foundation and SU2C for another two years of work. At MD Anderson, DePinho is committed to the team concept, but he’s also willing to defund or change the leadership of teams that don’t perform. The state of Texas, following the team model, passed a $3 billion bond issue to fund cancer research, but the program has been plagued by allegations of political intrigue and mismanagement.
The traditional researcher, sitting alone or with a couple of postdocs in a lab somewhere, working on that eureka moment, will always have a niche in this new ecosystem. “We still need people looking under rocks,” says Dr. William Nelson, director of the Johns Hopkins Cancer Center, a vice chairman of SU2C’s scientific-advisory committee and a successful rock looker underer, having discovered the most common genome alteration in prostate cancer. But the shift to team science is permanent. When he first considered SU2C’s team structure, Drebin was skeptical. “My feeling was that this was naiveté on the part of Hollywood executives,” he says. “You can make a movie this way. But not science. I take that back.”
It’s a new script for an old plot, and there is still a lot to be written as researchers learn more about the mutations driving most cancers. All we need now is the Hollywood ending.
With reporting by Alice Park