This week’s TIME magazine makes an eye-catching, bold proclamation. HOW TO CURE CANCER, the cover reads, with a subhead previewing the story contained inside: “Yes, it’s now possible – thanks to new cancer dream teams that are delivering better results faster.”
Much of that team science is happening right here at Penn Medicine, as part of Stand Up to Cancer’s pancreatic cancer “dream team.” As detailed in a News Blog post last fall before the third Stand Up to Cancer telethon, a Penn-led tumor tissue banking study is one of that dream team’s marquee achievements thus far. Since that trial began here, pieces of tumor from more than 60 patients with pancreatic cancer have kick-started a nationwide scavenger hunt that, bit by bit, is yielding new information that stands to shape a new, hopeful generation of treatments.
Under the direction of Jeffrey Drebin, MD, PhD, chairman of the department of Surgery in the Perelman School of Medicine, each patient’s tumor tissue is divided following their surgery and sent out to the other dream team institutions who study a variety of traits found within these tumors. Together, the team’s findings – essentially, the “secrets” of how pancreatic cancer cells use fuel inside the body, says Dr. Chi Dang, director of the Abramson Cancer Center -- are pooled and used to map out new treatment strategies.
“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.”
A CBS3 segment last fall explored the fruits of these efforts with a profile of a patient who, following surgery, enrolled in another Stand Up to Cancer study, which combines a chemotherapy drug with hydroxychloroquine, an anti-malarial medication that helps inhibit autophagy, a process smart cancer cells use to obtain nutrients from their environment to stay alive even after they’ve been damaged by chemotherapy and other treatments.
Hear more from Penn Medicine’s Stand Up to Cancer investigators including Dr. Drebin, Chi Van Dang, MD, PhD, and Peter O’Dwyer, MD: