Biomarkers, BEST Resource, and more
BEST (Biomarkers, EndpointS, and other Tools) Resource
Scientists from NIH and FDA have assembled an online collection of definitions for terms related to biomarkers and their use called BEST (Biomarkers, EndpointS, and other Tools). The BEST Resource
meets one of the goals set out in the 21st Century Cures Act, passed in December 2016 to develop a glossary of definitions related to biomarkers. The first question to be answered… “What is a biomarker?”
Scientists from NIH and FDA have assembled an online collection of definitions for terms related to biomarkers and their use called BEST (Biomarkers, EndpointS, and other Tools). The BEST Resource
meets one of the goals set out in the 21st Century Cures Act, passed in December 2016 to develop a glossary of definitions related to biomarkers. The first question to be answered… “What is a biomarker?”Blood pressure, serum cholesterol, and serum glucose are all 'biomarkers.' However, new technologies have resulted in an explosion of biomarker discovery. These new biomarkers generate confusion as to their potential uses and the validity of those uses. To reach agreement that a given biomarker was acceptable for a given use, scientists had to agree on the definitions of the types of biomarker and the types of use.
As an example, the BEST Resource defines a 'biomarker' as a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. This resource contains definitions for over 50 terms and concepts important for biomarker research and is designed to be regularly updated as new terms and concepts are introduced. View the BEST Resource.
Biomarkers and Diagnostic Tests: Qualification, Approval, and Role in Clinical Practice
NCTR scientists summarized very recent developments in the FDA's biomarker qualification program and contrasted biomarker qualification with companion diagnostic evaluation. While the term 'biomarker' is relatively new, (and has been defined concisely in the BEST Resource), the concept is millennia old. However, with the introduction of new technologies to discover potential biomarkers comes the need to assess their utility. This is particularly true for the use of biomarkers to support regulatory decisions in medical-product development. FDA has developed processes for the qualification of biomarkers and other medical-product development tools, underscored by recent legislation (i.e., the 21st Century Cures Act). This effort contrasts biomarker qualification with companion diagnostic evaluation and will be highly informative for researchers considering taking a biomarker discovery farther along the road to validation. A manuscript describing the study is available online at Experimental Biology and Medicine.
.Biomarkers and Diagnostic Tests: Qualification, Approval, and Role in Clinical Practice
NCTR scientists summarized very recent developments in the FDA's biomarker qualification program and contrasted biomarker qualification with companion diagnostic evaluation. While the term 'biomarker' is relatively new, (and has been defined concisely in the BEST Resource
), the concept is millennia old. However, with the introduction of new technologies to discover potential biomarkers comes the need to assess their utility. This is particularly true for the use of biomarkers to support regulatory decisions in medical-product development. FDA has developed processes for the qualification of biomarkers and other medical-product development tools, underscored by recent legislation (i.e., the 21st Century Cures Act). This effort contrasts biomarker qualification with companion diagnostic evaluation and will be highly informative for researchers considering taking a biomarker discovery farther along the road to validation. A manuscript describing the study is available online at Experimental Biology and Medicine.For more information, contact William Mattes, Ph.D., Director, Division of Systems Biology, FDA/NCTR.
Immune-Response Proteins as Biomarkers of Doxorubicin (DOX)-Induced Cardiotoxicity in Breast-Cancer Patients
In this pilot study, NCTR scientists identified proteins with significantly changed plasma levels in a group of breast-cancer patients who were treated with DOX-based chemotherapy and who later showed signs of cardiotoxicity. These proteins were associated with immune response and were identified before DOX treatment and/or at early doses of treatment; thus, they could be potential predictive biomarkers of cardiotoxicity. Although DOX has long proven to be useful in cancer treatment, it is known for its potential to induce cumulative dose-dependent cardiotoxicity. While it is critical to detect potential cardiotoxicity early—before onset of symptomatic cardiac dysfunction or heart failure—there are currently no biomarkers that can identify patients at risk of cardiotoxicity prior to or during the initial doses of chemotherapy.
In this pilot study, NCTR scientists identified proteins with significantly changed plasma levels in a group of breast-cancer patients who were treated with DOX-based chemotherapy and who later showed signs of cardiotoxicity. These proteins were associated with immune response and were identified before DOX treatment and/or at early doses of treatment; thus, they could be potential predictive biomarkers of cardiotoxicity. Although DOX has long proven to be useful in cancer treatment, it is known for its potential to induce cumulative dose-dependent cardiotoxicity. While it is critical to detect potential cardiotoxicity early—before onset of symptomatic cardiac dysfunction or heart failure—there are currently no biomarkers that can identify patients at risk of cardiotoxicity prior to or during the initial doses of chemotherapy.
In this study, plasma samples were collected before and after the first and second cycles of DOX-based chemotherapy from 27 breast-cancer patients. These samples were analyzed for the level of 83 proteins involved in immune responses or cardiovascular disease and several proteins were identified that may serve as biomarkers predicting poor heart function in DOX-treated patients. A manuscript describing the study is available online at Experimental Biology and Medicine.
. For more information, contact Li-Rong Yu, Ph.D., Division of Systems Biology, FDA/NCTR.
Contrast-Enhanced Imaging Used To Measure a Potential Biomarker of Drug-Induced Liver Injury (DILI)
NCTR scientists—as part of a study in collaboration with multiple pharmaceutical and academic laboratories—explored the use of gadoxetate (a gadolinium-based MRI-contrast agent) dynamic contrast-enhanced MRI to measure liver bile function, with promising results. The liver bile function was measured because in some cases, DILI is a result of the drug's effect on the liver's production of bile. The antibiotic, rifampicin, was used as a test drug in a rat study where both the uptake and excretion of gadoxetate were inhibited by the clinical dose of the antibiotic. The result and size of the effect was consistent across all participating laboratories. Therefore, this preliminary study suggests promise for liver bile function as a potential biomarker for DILI and may warrant further studies to determine its broader utility. A manuscript describing the study is available online at PLoS One.
Contrast-Enhanced Imaging Used To Measure a Potential Biomarker of Drug-Induced Liver Injury (DILI)
NCTR scientists—as part of a study in collaboration with multiple pharmaceutical and academic laboratories—explored the use of gadoxetate (a gadolinium-based MRI-contrast agent) dynamic contrast-enhanced MRI to measure liver bile function, with promising results. The liver bile function was measured because in some cases, DILI is a result of the drug's effect on the liver's production of bile. The antibiotic, rifampicin, was used as a test drug in a rat study where both the uptake and excretion of gadoxetate were inhibited by the clinical dose of the antibiotic. The result and size of the effect was consistent across all participating laboratories. Therefore, this preliminary study suggests promise for liver bile function as a potential biomarker for DILI and may warrant further studies to determine its broader utility. A manuscript describing the study is available online at PLoS One
.For more information, contact Serguei Liachenko, Ph.D., Division of Neurotoxicology, FDA/NCTR.
Altered MicroRNAs Identified in Serum of a Mouse Model of Parkinson’s Disease
In a study using a mouse model of Parkinson’s disease (PD), NCTR scientists identified four microRNAs that showed decreased expression in the blood compared to normal mice. This mouse model is like human PD—one of the deadlier neurodegenerative diseases of the elderly—because it shows a loss of dopamine brain cells and dopamine fibers. The presence of these microRNAs can now be further validated in large populations of PD patients to further evaluate their potential as biomarkers for PD. Because in PD-affected individuals, the motor symptoms do not typically appear until at least 70% of the neurons in the midbrain are either lost or damaged, it is important to search for new methods that aid in the early diagnosis of PD. Most PD cases are caused by a gene mutation; however, some toxicants such as MPTP— a contaminant found in street drugs—or high doses of pesticides can also cause PD in humans. MicroRNAs have emerged as potential biomarkers to help diagnose a variety of diseases, and NCTR is pursuing studies of microRNAs as biomarkers of PD. More information about this study can be found in Neuroscience Letters
.For more information, please contact Sumit Sarkar, Ph.D., Division of Neurotoxicology, FDA/NCTR.
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