MEDICAL: DISEASES: CANCER : MEDICAL: DIAGNOSIS: New Biomarker Method Could Increase the Number of Diagnostic Tests for Cancer

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MEDICAL: DISEASES: CANCER : MEDICAL: DIAGNOSIS: New Biomarker Method Could Increase the Number of Diagnostic Tests for Cancer

David P. Dillard


New Biomarker Method Could Increase the Number of
Diagnostic Tests for Cancer

Date: Mon, 29 Jun 2009 09:18:38 -0400
From: "NIH OLIB (NIH/OD)" <[hidden email]>
To: [hidden email]
Subject:  New Biomarker Method Could Increase the Number of
Diagnostic Tests for Cancer

U.S. Department of Health and Human Services

National Cancer Institute (NCI)

Embargoed for Release: Sunday, June 28, 2009, 1:00 p.m. EDT


NCI Office of Media Relations



[hidden email]


A team of researchers has demonstrated that a new method for detecting and
quantifying protein biomarkers in body fluids may ultimately make it
possible to screen multiple biomarkers in hundreds of patient samples,
thus ensuring that only the strongest biomarker candidates will advance
down the development pipeline.  The researchers have developed a method
with the potential to increase accuracy in detecting real cancer
biomarkers that is highly reproducible across laboratories and a variety
of instruments so that cancer can be caught in its earliest stages.

The results of the Clinical Proteomic Technology Assessment for Cancer
(CPTAC) study, which is sponsored by the National Cancer Institute (NCI),
part of the National Institutes of Health, and partner organizations,
appeared online June 28, 2009, in Nature Biotechnology.

"These findings are significant because they provide a potential solution
for eliminating one of the major hurdles in validating protein biomarkers
for clinical use.  Thousands of cancer biomarkers are discovered every
day, but only a handful ever makes it through clinical validation. This is
a critical roadblock because biomarkers have the potential to allow
doctors to detect cancer in the earliest stages, when treatment provides
the greatest chances of survival," said John E. Niederhuber, M.D., NCI
director.  "The critical limiting factor to date in validating biomarkers
for clinical use has been the lack of standardized technologies and
methodologies in the biomarker discovery and validation process, and this
research may solve that dilemma."

The collaborative and multi-institute nature of this work was critical
because many other technologies have yielded test results that vary
greatly from one laboratory to the next.  NCI's Clinical Proteomic
Technologies for Cancer (CPTC) program was established to help solve this
problem.  The five institutes that participated in this research as part
of the NCI-sponsored CPTAC include the Broad Institute of the
Massachusetts Institute of Technology and Harvard, Cambridge, Mass.;
Vanderbilt-Ingram Cancer Center, Nashville, Tenn.; University of
California, San Francisco; Purdue University, West Lafayette, Ind., and
Memorial Sloan-Kettering Cancer Center, New York City.

Proteomics studies interactions between proteins, which often work in a
tag-team fashion to send important signals within a cell.  Most proteomic
technologies have been based on mass spectrometry, a decades-old
technology that determines which proteins are in a specimen based on the
mass and electric charge of fragments of each protein.

The current biomarker discovery process typically identifies hundreds of
candidate biomarkers in each study using small numbers of samples, leading
to very high rate of invalid biomarkers.  The biomarkers that are actually
valid -- that is, true biomarkers -- must be culled from lengthy lists of
candidates, a time-consuming and not always accurate process.

The CPTAC center network study demonstrates that new applications of
existing proteomic techniques show promise of greater accuracy.  The
findings suggest that two technologies -- multiple reaction monitoring
(MRM) coupled with stable isotope dilution mass spectrometry (SID-MS),
which is a technique used by protein scientists to measure the abundance
of a particular protein in a sample -- may be suitable for use in
preclinical studies to rapidly screen large numbers of candidate protein
biomarkers in the hundreds of patient samples necessary for verification.

MRM provides a rapid way to determine whether a candidate biomarker is
detectable in blood.  This is critically important for clinical use, as
well as in being able to assess whether changes in a candidate biomarker
correspond with the presence or stage of a disease.  A sophisticated type
of mass spectrometry, MRM is designed for obtaining the maximum
sensitivity for quantifying target compounds in patient samples.

"Our work demonstrates that this technology has the potential to transform
how candidate protein biomarkers are evaluated.  SID-MRM-MS, combined with
complementary techniques, could provide the critical filter to assess
protein candidate performance without the immediate need for other
detection or quantification tests.  This would provide the critical
missing component for a systematic biomarker pipeline that bridges
discovery and clinical validation," said senior author Steven Carr, Ph.D.,
director of the Proteomics Platform at the Broad Institute. "This is an
important step forward for the field of proteomics, one that would not
have been possible without the collaborative efforts of the CPTAC

In this study, the researchers demonstrated that MRM is highly sensitive
and specific, important characteristics that ensure the detection of real
disease-specific biomarkers.  In addition, using common samples and
standardized protocols, they found that MRM is highly reproducible across
laboratories and technology platforms.  Clinical Proteomic Technologies
for Cancer will make common samples and standardized protocols available
through its reagents data portal, which can be accessed at


This new work grew from a memorandum of understanding between the NCI
(through Clinical Proteomic Technologies for Cancer) and the U.S. Food and
Drug Administration to accelerate proteomics technology development and
application in clinical settings.

CPTAC's goal is to empower the research community with the tools and
methods needed to translate proteomics from laboratory research to
clinical utility.  These efforts should have implications far beyond
cancer, ultimately affecting the diagnosis and treatment of much human

The full listing of participating institutes includes the Broad Institute
of the Massachusetts Institute of Technology and Harvard (with the Fred
Hutchinson Cancer Research Center, Massachusetts General Hospital, the
University of North Carolina at Chapel Hill, the University of Victoria
and the Plasma Proteome Institute), Memorial Sloan-Kettering Cancer Center
(with the Skirball Institute at New York University), Purdue University
(with Monarch Life Sciences, Indiana University, Indiana University-Purdue
University Indianapolis and the Hoosier Oncology Group ), University of
California, San Francisco (with the Buck Institute for Age Research,
Lawrence Berkeley National Laboratory, the University of British Columbia
and the University of Texas M.D. Anderson Cancer Center), and Vanderbilt
University School of Medicine (with the University of Texas M.D. Anderson
Cancer Center, the University of Washington and the University of

The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in
2003 to empower this generation of creative scientists to transform
medicine with new genome-based knowledge. The Broad Institute seeks to
define all the molecular components of life and their connections;
discover the molecular basis of major human diseases; develop effective
new approaches to diagnostics and therapeutics; and disseminate
discoveries, tools, methods and data openly to the entire scientific
community.  Founded by MIT, Harvard and its affiliated hospitals, and the
visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad
Institute includes faculty, professional staff and students from
throughout the MIT and Harvard biomedical research communities and beyond,
with collaborations spanning over a hundred private and public
institutions in more than 40 countries worldwide. For further information
about the Broad Institute, go to


Memorial Sloan-Kettering Cancer Center is the world's oldest and largest
private institution devoted to prevention, patient care, research, and
education in cancer. Their scientists and clinicians generate innovative
approaches to better understand, diagnose, and treat cancer. Their
specialists are leaders in biomedical research and in translating the
latest research to advance the standard of cancer care worldwide. For more
information, go to


The Purdue University-Indiana University Analytical Proteomics Team pairs
Purdue's experts in mass spectrometry and proteomics technology with the
expert clinical team of cancer researchers from Indiana University School
of Medicine. The team works to assess proteomic technology and its
applications for the diagnosis and treatment of cancer with a focus on
technology to diagnose breast and prostate cancer through blood samples.
The team is based at Purdue's Bindley Bioscience Center at Discovery Park.

UCSF is a leading university dedicated to promoting health worldwide
through advanced biomedical research, graduate-level education in the life
sciences and health professions, and excellence in patient care.

The Vanderbilt-Ingram Cancer Center is a NCI Comprehensive Cancer Center,
one of two centers in Tennessee and 40 in the country to earn this highest
distinction. Its nearly 300 faculty members generate more than $140
million in annual federal research funding, ranking it among the top 10
centers in the country in competitive grant support, and its clinical
program sees approximately 4,500 new cancer patients each year.
Vanderbilt-Ingram, based in Nashville, Tenn., recently joined with 21 of
the world's leading centers in the National Comprehensive Cancer Network,
a non-profit alliance dedicated to improving cancer care for patients
everywhere. For more information, visit


NCI leads the National Cancer Program and the NIH effort to dramatically
reduce the burden of cancer and improve the lives of cancer patients and
their families, through research into prevention and cancer biology, the
development of new interventions, and the training and mentoring of new
researchers. For more information about cancer, please visit the NCI Web
site at


or call NCI's Cancer Information Service at



The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and its
programs, visit




Addona T, Abbatiello SE, et al.
A multi-site assessment of precision and reproducibility of multiple
reaction monitoring-based measurements by the NCI-CPTAC Network: toward
quantitative protein biomarker verification in human plasma
Online June 28, 2009, Nature Biotechnology


This NIH News Release is available online at:

David Dillard
Temple University
(215) 204 - 4584
[hidden email]
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