Frontline Cancer: ‘Dream Team’ to study pancreatic cancer

FRONTLINE CANCER:

Pancreatic cancer may be the most devastating and lethal of all cancers. It comprises just 3 percent of all cancer cases in the United States. The average lifetime risk of developing it is roughly one in 67 or 1.5 percent, according to the National Cancer Institute. Yet, it is the fourth leading cause of cancer death, following lung, prostate and colon.

Just under 49,000 American men and women (evenly split) will be diagnosed this year with pancreatic cancer; just over 40,000 will die from the disease (7 percent of all cancer deaths).

Because pancreatic cancer occurs deep within the body, it is hard to detect early. Doctors can’t see or feel tumors during routine physical exams. There is no simple blood test for persons without symptoms. By the time symptoms appear, often caused by something else, the highly aggressive cancer has likely metastasized to other organs.

Without treatment, only one in five diagnosed patients will be alive one year later. With treatment, the median 5-year survival rate (patients alive five or more years after diagnosis) for all stages combined is just 6 percent.

These are the harsh facts at the moment, but maybe not in the future.

Recently, a team of physician-scientists at Moores Cancer Center at UC San Diego Health joined a first-of-its-kind international “dream team” of pancreatic cancer researchers and doctors — a three-year, $12 million effort to finally bring pancreatic cancer to “heal.”

Moores Cancer Center is joined by an impressive array of partners: the Salk Institute for Biological Studies, University of Pennsylvania, Princeton University, the Translational Genomics Research Institute and Mayo Clinic in the U.S. and the University of Cambridge, Queen Mary University and Barts Cancer Institute in the United Kingdom.

Most invasive pancreatic cancers develop mutations that allow cancer cells to acquire more nutrients than normal cells, fueling their growth and spread. Highly aggressive tumors also co-opt surrounding normal cells to help them extract additional resources.

Unlike other types of cancer, pancreatic cancers do not appear to rely upon glucose — a sugar — to survive and prosper, but rather use an amino acid called glutamine to produce the energy they need. Cancers that use glutamine as their energy source are frequently resistant to standard chemotherapy. Moreover, they can induce immune and other cells surrounding the tumor to produce growth factors that support the tumor’s ability to thrive.

The dream team, sponsored by Stand Up To Cancer (SU2C), Cancer Research UK and The Lustgarten Foundation, is targeting so-called “super-enhancers,” the bits of DNA that trigger the over-expression of genetic signals that aid and abet cancer growth. “This is a different approach to the disease,” said Andrew Lowy, M.D., chief of the Division of Surgical Oncology at Moores Cancer Center and one of the top pancreas surgeons in the world. “The idea is you might be able to reprogram pancreatic cancer cells to a different state so they can be less aggressive or you can create new vulnerabilities that can be exploited with combination drug therapies.”

The dream team, which includes international leader Ronald M. Evans, Ph.D., director of the Gene Expression Laboratory at Salk and an adjunct professor at UCSD, will take a three-pronged approach.

The first prong will develop new technologies to analyze pancreatic tumor super-enhancers to better understand how they exploit normal regenerative processes.

The second will investigate how pancreas cells obtain nutrients from nearby normal cells while evading detection by the immune system. The third will involve clinical trials using a new class of drugs that specifically target super-enhancers.

Joining Drs. Evans and Lowy is Tannishtha Reya, Ph.D., a professor in the UCSD School of Medicine’s departments of Pharmacology and Medicine and member of the Hematologic Malignancies Program at Moores Cancer Center. Dr. Reya studies how stem cell signals are subverted to make cancer cells resistant to therapy, resulting in relapse and recurrence. With Dr. Lowy and others, she will use new models to test treatments that may strip away drug-resistant cancer cells to help ensure a more durable disease remission.

The SU2C award is the third major grant Moores’ pancreatic cancer researchers have received this year.

Dr. Lowy’s team received a C3 Team Science award from Pedal the Cause funds designed, in part, to break down unique fibrotic tissue surrounding pancreatic cancer that prevents chemotherapy from reaching and killing it.

National Cancer Center also supports five NCI-designated cancer centers (including Moores, UC San Francisco and MD Anderson) to develop new ways to detect pancreatic cancer at an early, potentially curable stage, including genomic studies of the tiny pancreas cysts that are increasingly being detected by total body scans.

Pancreatic cancer is a recalcitrant disease. Clearly, new therapies are needed. The dream team can help make this a reality.

Scott M. Lippman, M.D., is director of UC San Diego Moores Cancer Center. His column on medical advances from the frontlines of cancer research and care appears in La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman at mcc-dir-lippman@ucsd.edu

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