Biomarkers: Cutting Edge Indicators to Assess Health,
Monitor Disease or Determine Responsiveness to Therapy
Moderator: A. Gregory Sorensen, MD, Director,
Center for Biomarkers in Imaging and Associate Director, Martinos Center for
Biomedical Imaging, MGH; Associate Professor of Radiology, HMS,
asorensen@partners.org
Metabolomic Approaches for Cardiovascular Biomarker Discovery
Robert Gerszten, MD, Principal Investigator,
Massachusetts General Hospital Center for Immunology and Inflammatory Diseases
(MGH CIID) and MGH Cardiovascular Research Center; Senior Associate Member,
Broad Institute; Associate Professor, Harvard Medical School,
rgerszten@partners.org
While decades of research
in biochemistry, nutrition, and physiology have revealed specific metabolic
pathways, systematic surveys of pathways altered in human disease states such
as atherosclerotic vascular disease are now possible. An emerging set of
technologies, based on mass spectrometry, enables "metabolomics,” the
monitoring of hundreds of metabolites from biological samples. These
technologies promise to transform our ability to profile samples with the goal
of illuminating biology and discovering valuable clinical biomarkers. In this
presentation, we will discuss the development of a targeted mass
spectrometry-based metabolomics platform, and its application to perturbation
studies in humans.
Video not yet available.
Imaging Biomarkers:
Uses, Misuses, Successes, and Failures
Homer Pien, PhD, Managing Director, Center for
Biomarkers in Imaging, MGH, hpien@partners.org
In the
mid-1980s two new drugs, flecainide and encainide, were introduced to reduce
ventricular arrhythmias in asymptomatic patients with histories of heart
disease. The drugs did indeed reduce
arrhythmias. A large trial was
undertaken to test the efficacy of the drugs, but the trial was stopped after a
year because patients taking the drugs were found to be almost two-and-half
times more likely to die than patients taking placebos. Flecainide and encainide were recalled in
1991. Their example demonstrates that
improving a biomarker does not necessarily translate into increased survival.
When
assessing clinical outcomes, one should think very carefully before using a
biomarker as a surrogate endpoint.
Biomarkers can be difficult to validate and require different levels of
validation depending on their intended use.
A good biomarker should accurately reflect a direct effect of an
intervention.
Many new
biomarkers are being developed that involve imaging technology. Noninvasive cardiac imaging techniques, for
example, are highly desirable and are actively being sought. Cardiac computed tomography (CT) has great
potential in this area, but its usefulness is currently limited by the fact
that calcium deposits in imaged tissue decrease the technique’s sensitivity and
specificity. To address this problem,
researchers funded by CIMIT have developed an iterative image reconstruction algorithm
that is able to successfully eliminate some of the “calcium blooming” that has
hampered the use of cardiac CT in the past.
Another new
imaging biomarker uses positron emission tomography (PET) to measure local
uptake of radiolabeled glucose. By
tracking glucose, doctors can find sites of inflammation, such as stenotic
arteries, because macrophages there take up glucose at high levels. Tumors also take up a lot of glucose, so the
imaging strategy can be used to monitor them as well. Tracking radiolabeled glucose is a promising
technique because it directly measures a step known to be crucial to
inflammation and tumor growth.
Imaging biomarkers have many advantages. They are usually noninvasive, and they
produce intuitive, multidimensional results.
They yield both qualitative and quantitative data and are relatively
comfortable for patients. To get as many
benefits as possible from imaging techniques, the data produced should be
combined with information from other sources.
Biomarkers will undoubtedly be useful in many ways, but clinicians and
researchers should resist the temptation to jump on the buzzword “bandwagon”
and should concentrate on the science behind the techniques.