and Medicine for Seniors
Deadly pancreatic cancer cells steered back into
Ability of treated
cancer cells to form tumors greatly diminished in test with mice
20, 2015 - Deadly pancreatic cancer cells were coaxed into reverting
back toward normal non-cancerous cells by a protein called E47. The
success of this new research provides hope for treatment of this disease
that kills 40,000 a year in the U.S.
“For the first time,
we have shown that overexpression of a single gene can reduce the
tumor-promoting potential of pancreatic adenocarcinoma cells and
reprogram them toward their original cell type. Thus, pancreatic cancer
cells retain a genetic memory which we hope to exploit,” said Pamela
Itkin-Ansari, Ph.D., adjunct professor in the Development, Aging, and
Regeneration Program at Sanford-Burnham and lead author of the study
published today in the journal Pancreas.
E47 turns the clock
E47 binds to specific
DNA sequences and controls genes involved in growth and differentiation.
The study, a
collaborative effort between Sanford-Burnham, UC San Diego, where
Itkin-Ansari holds a joint appointment, and Purdue University, generated
human pancreatic ductal adenocarcinoma cell lines to make higher than
normal levels of E47.
The increased amount
of E47 caused cells to stall in the G0/G1 growth phase, and
differentiate back toward an acinar cell phenotype.
In studies where the
reprogrammed cancer cells were introduced into mice, their ability to
form tumors was greatly diminished compared to untreated adenocarcinoma
adenocarcinoma is treated with cytotoxic agents, yet the average
survival for patients post-diagnosis is merely six months, and the
improvements in therapies are measured in days,” said Andrew M. Lowy,
M.D., professor of surgery at the UC San Diego Moores Cancer Center and
co-chair of the National Cancer Institute’s Pancreatic Cancer Task
“The finding that we
can differentiate these cancer cells back to a non-threatening phenotype
is encouraging. Indeed, there is a precedent for cell differentiation
therapy in that the approach has been used to treat acute promyelocytic
leukemia (APL) and some neuroblastomas successfully.”
“Our next step is to
test primary patient-derived tumor tissue to determine whether E47 can
produce similar results, potentially providing a novel therapeutic
approach to combat this highly lethal disease,” said Itkin-Ansari.
“Additionally, we are screening for molecules - potential drugs - that
can induce overexpression of E47.”
Pancreatic adenocarcinoma is the most common form of pancreatic cancer.
It’s primarily caused by a mutation in the oncogene called Kras that
causes the digestive enzyme-secreting cells (acinar cells) to
differentiate into a destabilized duct-like cell type, which is
The disease is often
called a “silent” cancer because it rarely shows early symptoms—it tends
to be diagnosed at advanced stages when it causes weight loss, abdominal
pain, and jaundice.
The study was funded
by support from the Hartwell Foundation, The Hirshberg Foundation,
National Cancer Institute, National Institutes of Health, National
Research Foundation of Korea and Yonsei University College of Medicine.