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TGen Discovers Potential Drug Targets That May Reduce Patient Pain Caused By Pancreatic Cancer

November 15, 2017

Pancreatic cancer is sometimes called the “silent disease”. That’s because symptoms most often do not present noticeably until the cancer has spread beyond the pancreas. The pain that comes with advanced-stage pancreatic cancer can become brutal as the cancer spreads and enlarging tumors puts pressure on sensitive nerves.

Besides the potential of causing extreme pain, pancreatic cancer has the worst average 5-year survival rate of any major type of cancer at 8.2% (2013 status) according to the National Cancer Institute. To give a staggering perspective on how devastating that statistic is, compare it to the average 5-year survival rate of female breast cancer of 89.7% (2013 status). Pancreatic cancer has a very low 5-year average survival rate that is almost 11 times worse than breast cancer.

Pancreatic cancer has surpassed breast cancer to become the 3rd leading cause of cancer deaths only ranking behind lung and colorectal cancers.

Existing Pancreatic Cancer Pain Control Methods

Presently there are several methods of pain control including pain medications such as morphine and various pain treatments that include nerve blocks by injecting nerve areas with an anesthetic. There are also medicines that destroy nerves at the pain source. Sometimes tumor sizes can be reduced with chemotherapy or radiation therapy which may relieve pressure on nerve areas.

A Pilot Pain Control Study May Lead To More Effective Treatment

TGen researchers have discovered a possible new and more effective pain control treatment method by targeting potential drug targets to reduce pancreatic cancer pain. This pilot study shows blocking nerve growth factor keeps cancer cells from invading surrounding nerves.

The following information provided by Steve Yozwiak of TGen describes the TGen study and its results.

TGen researchers have found that the nerve growth factor (NGF), a neurotrophic factor, and its receptor TRKA are associated with perineural invasion (PNI), which is the ability of pancreatic cancer cells to invade surrounding nerves.

Blocking the NGF signaling through inhibitors of NGF and TRKA reduces the potential of pancreatic cancer cells to migrate towards the surrounding nerves, according to a TGen study published in the scientific journal PLOS ONE.

“We have demonstrated that NGF signaling via the protein TRKA, between pancreatic cancer cells and surrounding nerves, is one of the molecular mechanisms involved in PNI,” said Dr. Haiyong Han, Associate Professor of TGen’s Clinical Translational Research Division and the senior author of the study.

One of the reasons for this disease’s dismal prognosis is due to the high rate at which the tumor recurs despite surgical removal. “A potential reason for the high rate of relapse has been postulated to be the ability of the pancreatic cancer cells to invade the surrounding nerves,” the study said.

This invasion is a highly coordinated process, involving signaling molecules secreted by both the nerves and the pancreatic cancer cells. The nerve ends are damaged and exposed by the pancreatic cancer cell invasion, resulting in pain.

The study found that this process also is associated with the growth and survival of pancreatic cancer cells. And, knocking down NGF or its receptors, TRKA and p75NTR, or treating TRKA with an inhibitor called GW441756, reduces the proliferation and migration of pancreatic cancer cells into the surrounding nerves.

The study concludes that additional research is needed, and that a clinical trial should be designed, using TRKA antagonists, to decrease the onset or worsening of pain for patients with advanced pancreatic cancer.

“We are trying to convince groups that have the TRKA inhibitor to allow us to test them in our systems and in the clinic as soon as possible,” said Dr. Daniel Von Hoff, TGen’s Distinguished Professor, Physician-In-Chief and a co-author of the study, who is one of the world’s leading authorities on this disease.

The study – Blocking Nerve Growth Factor Signaling Reduces the Neural Invasion Potential of Pancreatic Cancer Cells – was published October 28,, 2017 by PLOS ONE.

This study was funded, in part, by the National Cancer Institute, and by a grant from the Hearst Foundation.

Keyword Search Topics

This article covers the following related topics:: Pancreatic Cancer Pain Treatments, Pilot Study To Reduce Pancreatic Cancer Pain, TGen, and the Seena Magowitz Foundation.

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