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Penn Medicine at the Forefront of the Quest to Cure Cancer

Time cover 2
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This week’s TIME magazine makes an eye-catching, bold proclamation. HOWTO CURE CANCER, the cover reads, with a subhead previewing the storycontained inside: “Yes, it’s now possible – thanks to new cancer dream teamsthat are delivering better results faster.”

Muchof that team science is happening right here at Penn Medicine, as part of StandUp to Cancer’s pancreatic cancer “dream team.” As detailed in a NewsBlog post last fall before the third Stand Up to Cancer telethon, aPenn-led tumor tissue banking study is one of that dream team’s marqueeachievements thus far. Since that trial began here, pieces of tumor from morethan 60 patients with pancreatic cancer have kick-started a nationwidescavenger hunt that, bit by bit, is yielding new information that stands toshape a new, hopeful generation of treatments.

Underthe direction of Jeffrey Drebin, MD, PhD, chairman of the department of Surgeryin the Perelman School of Medicine, each patient’s tumor tissue is divided followingtheir surgery and sent out to the other dream team institutions who study a varietyof traits found within these tumors. Together, the team’s findings –essentially, the “secrets” of how pancreatic cancer cells use fuel inside thebody, says Dr. Chi Dang, director of the Abramson Cancer Center -- are pooledand used to map out new treatment strategies.

As TIMEwriter Bill Saporito details, those findings are yielding quick dividendsfor a cancer where tactics to improve survival has remained elusive for manyyears:

“The focus of the 28-personteam scattered across five institutions is to better understand the metabolicchanges that characterize pancreatic cells. It's a collaborative exercise thatstarts when surgeon Jeffrey Drebin of the University of Pennsylvania removes atumor 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 theSalk Institute's Gene Expression Laboratory, where researcher Geoffrey Wahl andcolleagues analyze the state of stellate, or star-shaped, cells that areusually 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 analyzesamino acids, sugar and up to 300 metabolites. Team members at Johns Hopkins andTranslational Genomics analyze the genome sequence.

One of the theories emergingfrom this group is that pancreatic cancer cells communicate with stellate cellsthat also show up around the tumor and conspire to ward off immune responsesand build resistance to chemotherapies. The tumor cells seem to leech glutamineand other amino acids from the rest of the body to feed the tumor--one reasonpeople with pancreatic cancer lose so much weight. Prevent the hijacking ofglutamine and other amino acids and perhaps the tumor starves. The team hasalso 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 analbumen-containing drug that shows promise in increasing the efficacy oftreatments. They enrolled 861 patients in a Phase III clinical trial of atreatment for advanced pancreatic cancer that adds the chemotherapy drugAbraxane, and the results have been encouraging: the combination stabilized thedisease 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.”

ACBS3 segment last fall explored the fruits of these efforts with a profileof a patient who, following surgery, enrolled in another Stand Up to Cancerstudy, which combines a chemotherapy drug with hydroxychloroquine, an anti-malarial medication that helps inhibitautophagy, a process smart cancer cells use to obtain nutrients from theirenvironment tostay alive even after they’ve been damaged by chemotherapy and othertreatments.

Hearmore from Penn Medicine’s Stand Up to Cancer investigators including Dr.Drebin, Chi Van Dang, MD, PhD, and Peter O’Dwyer, MD:



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