Pancreatic cancer is one of the most aggressive types of
malignancies, responsible for the deaths of nearly 42,000 Americans in 2016, and for the first time surpassing breast cancer as the
third-leading cause of cancer related death in the United States.
Many patients diagnosed with pancreatic cancer can succumb to the
disease in less than a year, and the majority of these patients suffer
from severe pain associated with their disease.
One of the reasons for this disease's dismal prognosis is due to the
high rate at which the tumor recurs despite surgical removal.
‘Blocking nerve growth factor (NGF) signaling through inhibitors of NGF and its TRKA receptor reduces the potential of pancreatic cancer cells to migrate towards the surrounding nerves.’
The Translational Genomics Research Institute (TGen) has discovered
potential drug targets to reduce pain in pancreatic cancer patients.
TGen researchers have found that 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.
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
"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 by PLOS ONE