Research Update Corner
By Mila McCurrach
Research Update Corner: Spring 2010
From global view to bird’s eye view, this installment of Research Update Corner reports on developments in pancreatic cancer research. As you will read, the momentum of pancreatic cancer genomics has caught an international wave on the heels of the landmark Pancreatic Cancer Genome Project, supported in part by The Lustgarten Foundation. I am also pleased to report on the near completion of the Foundation’s $1.25 million Early Detection Biomarker Initiative and tell you about additional activities that are forging progress in the fight.
Lustgarten Foundation Initiatives
Biomarker Initiative Nears Completion
In 2008, we told you about our Biomarker Development Initiative aimed at developing early detection and screening methods. The Initiative is comprised of a team of investigators representing four research institutions. Members were charged with developing antibodies for 60 candidate biomarkers. Biomarkers can be used to detect disease at very early stages and can even be used as tools to develop new therapies. We are pleased to report that the Initiative is nearly complete, with the successful development of antibodies for 40 of the 60 candidate biomarkers. Expanding the original scope of the Initiative, researchers began preliminary testing of some of the newly developed antibodies in the serum of pancreatic cancer patients to see if they show promise for early diagnosis. Plans are already underway for large-scale, in-depth screening studies that will be needed to test all of the new antibodies.
Australia Launches Pancreatic Cancer Genome Initiative
The Australian Pancreatic Cancer Genome Initiative (APGI) is a $27.5 million project designed to generate a comprehensive catalogue of genomic abnormalities in pancreatic cancer. The APGI is the Australian project arm of the International Cancer Genome Consortium (ICGC), which brings together leading scientists from across the world to catalogue genetic changes of the 50 most common cancer types and to accelerate research by making the data available to the entire research community rapidly and with minimal restrictions. The APGI is comprised of pancreatic cancer specialists from across the globe, and includes significant contributions from Johns Hopkins University, University of California San Francisco, and University of Verona, Italy. Learn more at www.garvan.org.au/apgi/overview.html.
Lustgarten-Funded Study Sparks Flurry of Activity
In the previous installment of Research Update Corner, an international team of investigators led by Lustgarten grantee Dr. David Tuveson of Cambridge Research Institute discovered a new mechanism that may explain why pancreatic cancer patients are often resistant to gemcitabine. The team analyzed a genetically modified mouse model of pancreatic cancer that closely resembles the human form of the disease, and as such, is largely resistant to gemcitabine. The study found that pancreatic tumors tend to have poor networks of blood vessels, called vasculature, which make it difficult for drugs to reach the tumor. This may help to explain why pancreatic cancer does not respond to drugs that starve the tumor by restricting its blood supply. The team also found that using a certain compound in conjunction with gemcitabine may facilitate delivery of the chemotherapy. This pivotal discovery set the stage for exciting follow-up studies, and already, there is a flurry of new activity lending support to Dr. Tuveson’s work.
For example, a study published in the New England Journal of Medicine found that blocking the Hedgehog signaling pathway with an experimental drug in a small group of patients with advanced basal cell carcinoma yielded a dramatic response, with some patients tumors shrinking weeks after starting the experimental drug. The basal cell carcinoma study is of particular interest to pancreatic cancer researchers because existing modeling systems have demonstrated that certain combinations of drugs cause pancreatic cancer cells to die. This new study suggests that Hedgehog inhibitors may offer a way to facilitate drug delivery in pancreatic cancer patients, allowing the drugs to reach the tumors.
Researchers from Johns Hopkins recently presented results of a mouse model study that may help explain why the addition of the drug nab-paclitaxel (Abraxane) in combination with gemcitabine may be more effective in combating advanced stage pancreatic cancer than gemcitabine alone. Results showed that adding nab-paclitaxel to gemcitabine may improve response to treatment in part by altering the supportive tissue around the tumor, allowing more gemcitabine to reach tumor cells. Mice that received the drug combination were twice as likely to respond to the treatment as those receiving gemcitabine alone. This study lends support to the theory that drug delivery plays an important role in treatment for pancreatic cancer. Nab-paclitaxel was recently granted orphan drug status by the FDA for use in patients with pancreatic cancer, and enrollment is underway for a phase III trial. Visit www.abraxisbio.com to learn more.
$18 Million SU2C Grant to Study Pancreatic Cancer Fuel Supply
The Translational Genomics Research Institute (TGen) and the University of Pennsylvania have received a three-year, $18 million grant from Stand Up To Cancer (SU2C) to investigate new approaches to treating patients with pancreatic cancer. Of five initial 'Dream Teams' selected for funding by SU2C, the TGen/Penn grant represents the largest award and the only project focused on pancreatic cancer. Using advanced imaging techniques, the Team seeks to develop tests that can determine what nutrients pancreatic cancer cells require to fuel their growth. The project scope also includes launching a series of clinical trials in advanced pancreatic cancer. Visit www.tgen.org to learn more.
Expert Panel Urges Smaller Initial Trials for Pancreatic Cancer
An expert panel convened by the National Cancer Institute (NCI) has recommended that pancreatic cancer clinical trials begin with small pilot studies before progressing to larger, more expensive studies. The panel also notes that a better understanding of signaling pathways and the role of the tumor microenvironment are needed, as are additional animal models. The report underscores a major and ongoing challenge to investigators: Developing better treatments for pancreatic cancer based on a limited knowledge of its biology. The report, Consensus Report of the National Cancer Institute Clinical Trials Planning Meeting on Pancreas Cancer Treatment, appeared online in the October 26 Journal of Clinical Oncology.
Cancer Protein Could Offer Insights into Treatment Response
A study published in Cancer Research by Dr. Jonathan Brody of Thomas Jefferson University and colleagues has found that gemcitabine, the standard of care for pancreatic cancer, may be more effective when a particular protein (HuR) is present. According to Dr. Brody, the HuR marker appears to provide insights into whether a patient will respond to treatment with gemcitabine. Although additional, largerscale studies are needed to further investigate this finding, the results of this initial study speak to an increasingly popular 'personalized medicine' approach to cancer care.
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