Pancreatic cancer: An update on a ‘stealth’ cancer
There’s been a steady stream of good news about cancer lately,
from targeted therapies like Gleevec to new strategies like anti-angiogenesis,
which zeroes in on the proliferating blood vessels that feed tumors.
But good news about pancreatic cancer is harder to come by. Doctors
haven’t yet discovered how to detect it early. Treatment has progressed
some, but there’s been nothing close to a breakthrough.
Now there’s a move to go back to medicine’s drawing board:
basic research. The hope is that a better understanding of the disease’s
genetics and molecular-level mechanisms will reveal an Achilles’ heel
and a target for more effective treatment. Early detection is another
goal because pancreatic cancer is rarely detected until it has spread
Symptoms can be vague
The pancreas has two functions — releasing fluids and enzymes
into the small intestine to aid digestion, and producing hormones (mainly
insulin and glucagon) that are instrumental to the body’s use of
Only about 10% of pancreatic cancers occur in the hormone-producing,
or endocrine, tissues known as the islets of Langerhans.
Far more common are cancers that originate in the tissues that produce
and deliver enzymes and digestive fluids.
Occasionally the disease does produce symptoms that serve as an early
warning. A tumor in the head of the pancreas can pinch off the bile duct,
so bilirubin from the liver and gallbladder back up into the bloodstream.
The resulting yellow discoloration of the skin and eyes — jaundice — accounts
for the majority of diagnoses that occur soon enough for surgery.
But many times, in its early stages, pancreatic cancer doesn’t
cause any symptoms. Those that do occur — abdominal discomfort,
weight loss, not being hungry — can be mistaken for indigestion
or some other minor gastrointestinal problem.
Not many risk factors
Smoking is one well-established risk factor. Smokers are two to three
times more likely to get pancreatic cancer than nonsmokers are. Some
studies have implicated high-fat diets.
Pancreatic cancer is clearly linked to some forms of chronic pancreatitis,
which has various causes, including alcohol abuse. But whether there’s
a connection between alcoholism and pancreatic cancer is far from clear.
Isolated cases of acute pancreatitis, such as those caused by gallstones,
don’t appear to increase risk for the disease.
Incidence is holding steady
Eleventh among cancers in the number of new cases diagnosed each year
(the incidence), pancreatic cancer isn’t the most common type of
cancer. It is, though, one of the deadliest, ranking fourth among cancers
in the number of deaths it causes. The median survival time is about
One bright spot is that its incidence has been level despite demographic
trends that would tend to pull it up.
Like many cancers, pancreatic cancer is an older person’s disease:
80% of those diagnosed with it are older than 60. Because of increased
longevity and the aging of the baby boom generation, the number of older
Americans is growing rapidly.
Pancreatic cancer can be treated surgically by removing the tumor if
the cancer hasn’t spread to blood vessels, distant lymph nodes,
other organs — a big if, given that it’s so often diagnosed
late. Fewer than 20% of pancreatic tumors can be removed surgically.
A major change in treatment occurred with the introduction of the chemotherapy
drug gemcitabine (Gemzar) for postsurgical use. Gemcitabine (pronounced
jem-SITE-a-bean) is in a class of medications known as antimetabolites
that work by interfering with cancer cell growth. It’s used after
surgery to keep the cancer from coming back.
Sadly, the bottom line is that no matter what the treatment, about 75%
of patients who have surgery will die of recurrent disease within three
to four years.
One reason that pancreatic cancer may be so hard to treat is that the
pancreas is not encased in a membrane as other organs are. This “nakedness” may
make local spread more likely. In addition, pancreatic tumors also get
cocooned in scarlike tissue that creates a low-oxygen environment, which
makes radiation and chemotherapy less effective. Lastly, the genes of
pancreatic cancer cells have multiple mutations, which may be why they
can fend off chemotherapy drugs so well.
Gain against pain
When pancreatic cancer can’t be treated surgically, doctors do
their best to ameliorate symptoms and help people live a little longer.
If, for example, the pancreatic tumor is obstructing the bile duct or
gastric outlet, doctors can open the blockage with a stent or surgical
Back to basics
Genetic studies. Pancreatic cancer does run
in some families. Researchers have found that pancreatic cancer is more
common in families with several rare inherited cancer syndromes (Peutz-Jeghers
to name one) that until recently weren’t associated with the disease.
Researchers have recently discovered that mutations in the BRCA2 gene,
first identified as a breast and ovarian cancer gene, may also be a cause
of pancreatic cancer.
In December 2006, the field of pancreatic cancer genetics got its most
exciting news in years: Research identified the first gene specifically
implicated as a cause of pancreatic cancer — a mutated palladin
The palladin gene produces a protein that makes up the cell walls. The
protein generated by the mutated version may permit those cells to move
faster than normal cells, which could explain why pancreatic cancer spreads
so rapidly to other parts of the body.
Early detection. An especially exciting area
of research involves the search for substances that could aid in spotting
pancreatic cancer earlier. The mutated palladin gene — or the protein
it expresses — might serve as such a biomarker.
There’s considerable interest in certain growth-regulating proteins
that appear to play a role in the underlying mechanism of pancreatic
cancer and might be used for early diagnosis.
So far none of the imaging technologies — CT scans, MRIs, ultrasound — have
been shown to work for screening. But there are ongoing studies in high-risk
individuals, which may show that a combination of tests will be useful
in finding abnormal growths early.
Researchers think there may be an extended precancerous stage when lesions
known as pancreatic intraepithelial neoplasias are localized. It’s
possible these lesions release a protein into the blood that will be
useful in screening and early detection.
April 2007 update
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