New strategy to improve drug delivery to pancreatic tumors

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New strategy to improve drug delivery to pancreatic tumors

The March 20, 2012 issue of the prominent journal Cancer Cell published an important study out of the laboratory of a two-time Pancreatic Cancer Action Network research grant recipient. Sunil Hingorani, MD, PhD received the Dr. Laurence A. Mack and Roselle Mack Memorial Career Development Award in 2005 and a Pilot Grant in 2007 from the organization. Dr. Hingorani is currently an associate member of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr. Hingorani’s work focuses on the vasculature (blood vessels) that are associated with pancreatic tumors. Unlike many other solid cancer types, pancreatic tumors do not create new blood vessels, a process known as angiogenesis. The formation of new blood vessels in other types of cancer ensures proper blood supply to the tumor, delivering nutrients and oxygen. Instead, pancreatic tumors are able to survive with poor vasculature and under very low oxygen conditions. Part of the reason that pancreatic tumors cannot make new blood vessels is because of the dense microenvironment, the tissue that surrounds and infiltrates the tumors. Dr. Hingorani and colleagues have also shown that the pressure from the thick microenvironment presses on existing blood vessels and blocks blood flow.

Since chemotherapeutics and other cancer drugs are administered intravenously, the poor blood supply to pancreatic tumors also impedes drug delivery. A mouse model of pancreatic cancer that Dr. Hingorani helped develop mimics this feature of human pancreatic cancer. Researchers have observed that when the mice are treated with gemcitabine, the standard of care chemotherapy for pancreatic cancer, the drug is unable to reach the tumor.

In this study, Dr. Hingorani and colleagues evaluated a drug that could alleviate some of the pressure of the microenvironment and strengthen the blood supply to pancreatic tumors, allowing drugs to reach, and kill, the cancer cells. Specifically, a compound called hyaluronic acid (HA) plays a pivotal role in preventing functional blood vessel formation. Therefore, the research team’s strategy is to utilize a drug (called PEGPH20) that targets HA. By targeting HA, PEGPH20 relieves the pressure on the blood vessels and allows better blood flow to the tumor. Administering PEGPH20 in combination with other therapeutic drugs, like gemcitabine, will hopefully increase drug delivery to the tumor by opening up the blood vessels, and cause cancer cell death.

Researchers at the Cancer Research UK in Cambridge found similar results when testing PEGPH20 for pancreatic cancer and published their findings in the journal Gut this week as well.

Based on the preclinical data, PEGPH20 is currently in early clinical trials in the US and Europe.

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 Associates are available M-F 7am-5pm Pacific Time.

Click here to read the scientific abstract of this study.

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