AACR Special Conference – Pancreatic Cancer: Progress and Challenges

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Research in the News

News from the first Pancreatic Cancer Special Conference hosted by the American Association for Cancer Research

For the first time, the American Association for Cancer Research (AACR) hosted a special conference completely devoted to pancreatic cancer, which took place June 18-21, 2012 in Lake Tahoe, NV. The Pancreatic Cancer Action Network proudly served as the lead supporter of this meeting. Over 400 scientists were in attendance to share results, form collaborations, and brainstorm about new approaches and strategies to fight pancreatic cancer.

The results reported below are exciting advances in our understanding of pancreatic cancer presented at this meeting. Some represent experiments conducted in the laboratory, studying cells in a dish or mouse models of pancreatic cancer. Others are describing clinical trials, testing ideas from the laboratory in patients. But please note that additional studies will be required before these discoveries will impact the majority of pancreatic cancer patients. They must meet the rigorous but reasonable standards of being safe and providing an improvement over current clinical practices that are required to change the way we detect or treat pancreatic cancer.

The Pancreatic Cancer Action Network encourages all patients to consider clinical trials when exploring treatment options. For more information about ongoing clinical trials or any other questions about pancreatic cancer treatment or diagnosis, please contact a Pancreatic Cancer Action Network Patient and Liaison Services (PALS) Associate toll-free at 877-272-6226 or email pals@pancan.org. PALS Associates are available M-F 7am-5pm Pacific Time.

Here are a few examples of exciting research being presented at this meeting.

A diet high in fat and calories accelerates pancreatic cancer development in mice
This study was performed by a group of University of California, Los Angeles researchers, including David Dawson, MD, PhD, recipient of the 2008 Seena Magowitz Pancreatic Cancer Action Network Career Development Award. Mice that are genetically programmed to develop pancreatic cancer were fed either a diet high in fat and calories, or a normal diet. Those fed the higher fat diet developed pancreatic cancer sooner than the mice fed with the control food.

Understanding response and resistance to a novel treatment strategy
The novel targeted drug BAY 86-9766 was explored as a treatment option in mice programmed to develop pancreatic cancer. The mice initially responded well to the drug, but then the disease returned. The mouse model allowed examination of the features leading to relapse, to try to prevent this response in the future.

A protein shown to be involved in inducing aggressive behavior of pancreatic cancer cells
This work was conducted primarily in the University of California, San Francisco laboratory of Frank McCormick, PhD, recipient of the 2010 Fredman Family Foundation Pancreatic Cancer Action Network Innovative Grant and member of the Pancreatic Cancer Action Network’s Scientific Advisory Board, with collaboration from Eric Collisson, MD, recipient of the 2012 Skip Viragh Pancreatic Cancer Action Network Career Development Award. Here, the researchers demonstrate that K-Ras, the most commonly mutated protein in pancreatic cancer, also causes pancreatic cancer cells to be converted to a more aggressive type of cell, known as a cancer stem cell, and this process is mediated by a protein called leukemia inhibitory factor.

Pancreatic cancer treatment option that targets most aggressive cells
Pancreatic cancer stem cells are thought to be responsible for allowing the tumor to form metastatic lesions in distant organs, and are also especially resistant to conventional therapies. Researchers in Madrid combined a drug called metformin (also used to treat diabetes) with the chemotherapy gemcitabine, to target both the highly aggressive cancer stem cells and the bulk tumor cells, in a mouse model of the disease.

Testing a novel combination of various types of treatment
MD Anderson Cancer Center authors of this study include Christopher Crane, MD and Jason Fleming, MD, both members of the Pancreatic Cancer Action Network’s Medical Advisory Board. A Phase I clinical trial evaluated the safety and appropriate doses of the combination of targeted therapies bevacizumab and erlotinib, in combination with the chemotherapy drug capecitabine and radiation therapy.

Discovering a panel of biomarkers to aid in the diagnosis of pancreatic cancer
The researchers evaluated candidate biomarkers, proteins from a blood sample that could diagnose pancreatic cancer, and compared their expression in patients to samples from individuals with pancreatitis or healthy controls. The biological and mathematical results suggest that a panel of 40 biomarkers that individually only weakly signify pancreatic cancer presence might be able to provide a desirable level of specificity when measured together.

A treatment regimen that capitalizes on pancreatic tumors’ low oxygen environment
Pancreatic tumors are able to grow under very low oxygen conditions. This characteristic makes the cancer cells especially aggressive, and also contributes to their ability to resist being killed by many kinds of cancer treatment. This study involves combining a drug, called TH-302, which particularly targets cells in a low oxygen environment, with radiation therapy, in a mouse model of pancreatic cancer.

Subtle changes in gene coding for the vitamin D receptor may influence pancreatic cancer outcome
This research team includes Gloria Petersen, PhD, member of the Pancreatic Cancer Action Network’s Scientific Advisory Board. The authors searched for subtle genetic changes that may impact the survival rates of individuals with pancreatic cancer, and found such changes in the gene that codes for the vitamin D receptor.

Novel treatment combination targets pancreatic cancer stem cells
This presentation describes an early-stage clinical trial conducted by researchers at the University of Michigan, led by Diane Simeone, MD, recipient of the 2010 The Randy Pausch Family Pancreatic Cancer Action Network Innovative Grant and member of the Pancreatic Cancer Action Network’s Scientific Advisory Board. Dr. Simeone and colleagues are testing an inhibitor of a protein pathway called hedgehog that is known to be activated in pancreatic cancer cells, specifically a very important subset of cells known as cancer stem cells.

Drug target that may increase pancreatic tumors’ response to chemo- and radiotherapy
A protein called RLIP76 has been shown to allow cancer cells to escape death, and also promotes the removal of toxic drugs that would otherwise threaten the cancer cells. Therefore, this team of researchers sought to block the expression of RLIP76 in a mouse model of pancreatic cancer, and determine whether the cancer cells became more susceptible to death by chemotherapy or radiation treatment.

A mouse model helps explain pain experienced by pancreatic cancer patients
In mice genetically programmed to develop pancreatic cancer, scientists discovered that nerve-related factors were released that stimulate intense pain in the vicinity of the tumor. The researchers confirmed this result by evaluating some behavior and physical activity levels of the mice with tumors, compared to healthy mice.

Link between exposure to the sun and risk of developing pancreatic cancer
This study took place in Australia, and the data suggest that individuals born in a location with high exposure to the sun’s ultraviolet rays were at a lower risk of developing pancreatic cancer, compared to people born somewhere with less sun exposure. Further, individuals with lighter, more sun-sensitive skin were also observed to have a lower risk of the disease. This observation is thought to be independent on vitamin D levels, which are increased upon sun exposure.

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