Currently, the prognosis for pancreatic adenocarcinoma, the
most common form of cancer affecting this enzyme secreting organ, is
not great. Despite accounting for roughly 85% of diagnoses, the survival
rate is a mere six months, and the improvements caused by therapies are
measured in just days.
A new study
has, however, shown that pancreatic adenocarcinoma cells can be coaxed
to revert back to normal cells—a discovery that could possibly lead to
new treatment therapies. The research was carried out in a collaborative effort between Sanford-Burnham, UC San Diego, and Purdue University, and published last week in the journal Pancreas.

"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," said Pamela Itkin-Ansari, an adjunct professor at Sanford-Burnham
and author of the study. "Thus, pancreatic cancer cells retain a
‘genetic memory’ which we hope to exploit."
The team started off by growing human pancreatic cancer cells in the
lab, and then inducing them to produce more of a protein called E47.
This protein binds to a specific sequence of DNA that controls the genes
involved in growth and differentiation.
As a result, the cells stalled in their growth phase and began to
revert back to non-cancerous cells. They were then able to take the
reprogrammed cancer cells and introduce them into mice, where their
ability to form tumors was greatly reduced.
The main reason that pancreatic cancer has such a poor prognosis and
low survival rate is because it is typically diagnosed at a late
stage. This means that by the time it's found, it is often too late for
treatment to be effective, and it has likely already spread to other
parts of the body. This is due to the fact that the most common symptoms
that result—weight loss, abdominal pain, and jaundice—usually only
occur after the tumor is a significant size. Another aspect is that the
nature of the tumor cells is one that is incredibly aggressive, able to
hide out and spread rapidly.
Patients with pancreatic adenocarcinoma are currently treated using
so called "cytotoxic agents" that work by killing or interfering with
some aspect of how the cancer cells divide and multiply. The medicine
works best on cells that rapidly divide. Since, in general, cancerous
cells divide at a much higher rate than normal body cells, they are
normally predominantly affected. However, the treatment is not perfect
as there are some types of normal body cells, such as bone marrow, which
also divide rapidly and are thus unintentionally targeted, leading to
side effects.
The researchers hope that their discovery could lead to a new therapy
for pancreatic cancer that would subvert these problems. "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,” explained Andrew M. Lowy, professor of surgery at UC San
Diego.
The next stage is to test patient-derived cancer cells to see if E47
has a similar effect in stopping the tumor growth as those seen in the
lab. In addition to this, they will start screening for molecules that
have the potential to ramp up the production of E47 in cells.
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