Early
Detection of Pancreatic Cancer
Introduction
Pancreatic cancer is diagnosed
primarily through the use of computed tomography (CT) scans, endoscopy,
laparascopy, biopsy and exploratory surgery. Unfortunately, these
tests are ineffective at detecting smaller lesions, pre-cancers
or early stage cancers, which may be more amenable to a cure.
When diagnosed early, surgical resection offers the best chance
for long term control of the disease, yet nearly 90% of patients
are diagnosed with metastatic cancer and are not eligible for such
a procedure. Tests sensitive enough to detect pancreatic cancer
in the earliest stages before symptoms develop are therefore urgently
needed. For individuals who are at increased risk due to family
history and chronic or hereditary pancreatitis, effective early
screening methods are especially important.
A blood test, because of
ease of use, cost effectiveness and patient compliance, is the ideal
early detection method. In prostate cancer, the PSA test identifies
a specific substance or biomarker in the blood that, at certain
levels, is highly indicative of cancer. At institutions across
the country, the search is on for pancreatic cancer biomarkers that
can be used in a diagnostic test. Researchers are using a variety
of methods to find these markers and they are beginning to yield
promising results.
Current Research
Using genetic analysis, scientists
are looking for specific genes and changes within genes that are
associated with pancreatic cancer. Preliminary studies have revealed
that a significant number of genes are upregulated, or abnormally
active, in pancreatic cancer cells. Some of this increased gene
expression can be detected not only in tumor biopsy samples, but
also in pancreatic juice (digestive fluids secreted by the pancreas).
Researchers predict that they will be able to isolate them in
blood samples as well. Other studies have identified a genetic
alteration, called methylation, in pancreatic cancer cells that
also can be detected in pancreatic juice. Studies with larger
numbers of test subjects are required to confirm these results and
refine their ability to predict pancreatic cancer.
Proteomics is a new and exciting
area of research that involves analyzing samples of biological fluids
for patterns of protein expression unique to a specific disease.
For example, a small study done at Johns Hopkins analyzed pancreatic
juice taken from patients undergoing pancreatic resection for either
adenocarcinoma or other non-cancerous diseases. Protein from each
sample was bound to a specialized biochip, which was then analyzed.
The samples from the cancer patients contained elevated levels
of a protein that was not detected in the non-cancer group. Research
is continuing at Johns Hopkins to see if collections of pancreatic
juice taken from pancreatic cancer patients and high-risk individuals
during endoscopic screenings yield similar results.
Proteomic methods are also
showing promise in finding a biomarker in blood. A collaborative
effort by researchers at the University of Pennsylvania and the
National Institutes of Health has revealed a reproducible protein
pattern in the blood of mice bred to develop early stage pancreatic
cancer lesions called Pancreatic Intraepithelial Neoplastic ( PanIN)
lesions . A large study is now underway to determine if this protein
pattern corresponds to early or late stage pancreatic cancer in
humans.
A diagnostic test involving
any biomarker must be able to distinguish between an affected and
unaffected individual with near 100% accuracy. It is doubtful
that one marker alone will be specific enough to reliably diagnose
pancreatic cancer; more likely, a group, or panel, of many markers
will be combined to create an accurate test.
Existing Options
Until a reliable early detection
test is developed, there needs to be a screening protocol for high-risk
individuals. Although many doctors agree that having two or more
close family members with pancreatic cancer constitutes high risk,
there is no consensus as to when, how often and with what methods
these individuals should be screened. At the International Symposium
on Inherited Diseases of the Pancreas in November, experts hope
to form guidelines.
Because of the lack of knowledge
surrounding early screenings, doctors stress the importance of taking
part in investigational studies targeted specifically at populations
at high risk for pancreatic cancer. A few institutions already
have programs in place and others are in the process of developing
them. Over the next few years, they will provide a wealth of information
regarding who is at risk, what genes are most involved and the best
methods for early diagnosis and treatment. Most involve monitoring
high-risk persons using endoscopic ultrasound (EUS), CT scans and/or
ERCP (Endoscopic Retrograde Cholangiopancreatography), if needed.
Participants may also undergo novel imaging procedures, be tested
for genes associated with hereditary pancreatic cancer, and have
biological fluids, such and blood and pancreatic juice, collected
and analyzed. Besides the advantage of having screenings performed
by knowledgeable doctors and possibly benefiting from cutting edge
diagnostic tests, study participants will undoubtedly help advance
the science of early detection.
With continued research,
improved technology and increased funding, researchers predict that
significant advances in the early detection of pancreatic cancer
will be made in the next few years.
If you have questions
about early detection of pancreatic cancer, please contact a PanCAN
Patient and Liaison Services (PALS) Associate toll-free at 877-272-6226
or by email at pals@pancan.org
.
PanCAN thanks the following
doctors for their important contributions to this column:
Randy Brand, MD, Evanston
Northwestern Healthcare
James Disario, MD, University
of Utah
Michael Goggins, MD, Johns
Hopkins University
Samir Hanash, MD, PhD, University
of Michigan
Gloria Petersen, PhD, Mayo
Clinic
Craig Logsdon, PhD, University
of Michigan
David Tuveson, MD, PhD, University
of Pennsylvania
|
