A cancer scientist from Johns Hopkins has convinced an international
group of colleagues to delay their race to find new cancer biomarkers
and instead begin a 7,000-hour slog through a compendium of 50,000
scientific articles already published to assemble, decode and analyze
the molecules that might herald the furtive presence of pancreatic
With limited resources available for the exhaustive and expensive
testing that needs to be done before any candidate can be considered a
bona fide biomarker of clinical value, it’s important to take stock of
the big picture and strategize, says Akhilesh Pandey, M.D., Ph.D., an
associate professor in the McKusick-Nathans Institute of Genetic
Medicine, Johns Hopkins University School of Medicine, and founder and
director of the Institute of Bioinformatics in Bangalore, India.
Having mined the literature to amass 2,516 potential biomarkers of
pancreatic cancer, Pandey and his team are publishing their compendium
on April 6 in PLoS Medicine. They systematically cataloged the genes
and proteins that are overexpressed in pancreatic cancer patients, then
characterized and compared these biomarker candidates in terms of how
worthy each is of further study.
More than 200 genes are shortlisted because they were reported in
four or more published studies to be overexpressed —– meaning that the
proteins they make are in higher abundance in people with pancreatic
cancer than in people without the disease. This qualifies them as
"excellent candidates" for the further studies that are needed to
validate them as sensitive and specific biomarkers, note the authors.
Pandey says he was motivated by the fact that even leading cancer
investigators had no real idea about how many candidate biomarkers for
pancreatic cancer had already been identified, much less how they
stacked up against each other in terms of clinical value in detecting
early stages of the disease. Such biomarkers are highly valued because
they gallop Paul Revere-like through the bloodstream and can signal
early warnings of clinically invisible cancers and other diseases.
"Curation and databases are not very sexy concepts," says Pandey.
"But we can’t keep doing the exciting new discovery stuff and never
take the time to catalog our results and share them."
Taking pancreatic cancer biomarkers to prove the value of such a
strategic "big picture" approach, Pandey says it could serve as a basis
for other disease-marker research.
"For the first time with pancreatic cancer — and potentially with
any cancer — we have a handle on the number of candidates already
identified and a real sense of how big an army we should send on the
mission of further testing them," says Pandey.
Pandey’s ultimate goal is to ferret out the best protein biomarker
for pancreatic cancer — a molecule that reveals itself in an accessible
bodily fluid and therefore can be detected with ease and accuracy —
just like the protein biomarker that’s made early on by a developing
fetus and is exploited by at-home pregnancy tests.
The "gold standard" pancreatic cancer biomarker would possess both
high sensitivity and specificity for early diagnosis. Cancer, at its
most basic, is an abnormal population of cells that produce specific
molecules — biomarkers — which healthy, cancer-free bodies do not.
Cancer also tends to be incipient, Pandey says.
The ideal biomarker would allow for easy diagnosis when a cancer is
still young, before it spreads to other organs. It could also help
clinicians make informed decisions about treatments and better predict
of outcomes, Pandey says: "Biomarkers could tell us who should undergo
surgery, who should get chemotherapy, and in which people a cancer is
likely to recur."
Biomarker discovery is an exploding area of research, Pandey says,
yielding ever-increasing amounts of data — more than any one person can
hope to keep track of, unless it’s all strategically collected for
"We want to initiate a trend by proving the importance of collection
and cataloging," Pandey says, "which are exercises that many might view
The team’s next step is to create a searchable Web database that is universally available and free.
The research was supported in part by the Lustgarten Foundation for Pancreatic Cancer Research.
Authors of the paper, in addition to Pandey, are H.C. Harsha and
Arivusudar Marimuthu of the Institute of Bioinformatics, Bangalore,
India; Manipal University, Karnataka, India; and McKusick-Nathans
Institute of Genetic Medicine, Johns Hopkins University. Also, Kumaran
Kandasamy, Suresh Mathivanan, and Manoj Kashyap of the Institute of
Bioinformatics, Bangalore, India, and the McKusick-Nathans Institute of
Genetic Medicine, Johns Hopkins University. Prathibha Ranganathan,
Sandhya Rani, Subhashri Ramabadran, Sashikanth Gollapudi, Lavanya
Balakrishman, Sutopa B. Dwivedi, Deepthi Telikicherla, Lakshmi Dhevi N.
Selvan, and Renu Goel, of the Institute of Bioinformatics, Bangalore,
India; Robert Vizza of The Lustgarten Foundation for Pancreatic Cancer
Research, New York; Robert J. Mayer and James A. DeCaprio of the
Dana-Farber Cancer Institute, Boston; Sudhir Srivastava of the Cancer
Biomarkers Research Group, NIH; Samir M. Hanash of the Fred Hutchinson
Cancer Research Center, Seattle; and Ralph H. Hruban of the Departments
of Pathology and Oncology at the Sol Goldman Pancreatic Cancer
Institute, Johns Hopkins.
Source : Johns Hopkins Medical Institutions