Translational Biomarkers: from Preclinical to Clinical a Report of 2009 AAPS/ACCP Biomarker Workshop

Abstract

Abstract. There have been some successes in qualifying biomarkers and applying them to drug development and clinical treatment of various diseases. A recent success is illustrated by a collaborative effort among the US Food and Drug Administration, the European Medicines Agency, and the pharmaceutical industry to provide a set of seven preclinical kidney toxicity biomarkers for drug development. Other successes include, but are not limited to, clinical biomarkers for cancer treatment and clinical management of heart transplant patients. The value of fully qualified surrogate endpoints in facilitating successful drug development is undisputed, especially for diseases in which the traditional clinical outcome can only be assessed in large, multi-year trials. Emerging biomarkers, including chemical genomic or imaging biomarkers, and measurement of circulating tumor cells hold great promise for early diagnosis of disease and as prognostic tests for managing treatment of chronic diseases such as osteoarthritis, Alzheimer disease, cardiovascular disease, and cancer. To advance the success of treating and managing these diseases, efforts are needed to establish the temporal relationship between changes in inflammatory or imaging biomarkers with the progression of the chronic disease, and in the case of cancer, between the extent of circulating cancer cells and tumor progression or remission.

Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside

“…Figure 2 shows a strategic flowchart illustrating the application of gene expression in drug discovery and development. The statistical rigor in qualifying a specific gene-expression signature as a biomarker depends on its fit-for-purpose use (90,91) and will become more stringent the further along a drug development program moves. In fact, when the gene-expression signature is used as an efficacy or safety marker in late-stage drug development, the quantitative rigor needs to meet appropriate assay characterization for any other clinical parameter measured.…”

“…The pertinence of a gene-expression signature qualified for advancing a drug candidate or for predicting the safety profile of a drug relies on an array of scientific supportive evidence (90,93) and depends on its statistical association with the functional, structural, and phenotypic changes following exposure to a drug, as illustrated in Fig. 3.…”

Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

“…A biomarker (a little over 30 years old medical terminology) represents an indicator of a peculiar biological state that can objectively measure and compare normal biological and pathogenetic processes, or pharmacological responses to a therapeutic intervention [21]. Originating from tissues or body fluids, biomarkers may be potentially used as a risk factor and/or a useful tool to classify physio-pathologic conditions, to obtain basic informations underlying the pathogenetic mechanism(s) of human diseases, to detect cancers early, and to guide the choice of therapy [22].…”

“…The hot topic of cancer biomarkers has been recently debated [17,19-21,24]; among well-known biomarkers, uPA/PAI combination has long been regarded as prognostic indicator of BC, widely confirmed by prospective, retrospective and meta-analysis studies [49]. Nevertheless, uPA/PAI test has not been widely adopted in clinical practice, mainly linked to the fact that “ Clinicians usually prefer to over-treat some BC patients, instead of using prognostic biomarkers with less than perfect prediction ” [20].…”

Treatment of Knee Osteoarthritis with Autologous Expanded Bone Marrow Mesenchymal Stem Cells: 50 Cases Clinical and MRI Results at One Year Follow-Up

“…The FDA (Federal Drug Administration) together with the OARSI (Osteoarthritis Research Society International) established the OARSI-FDA Biomarkers Working Group. They published a comprehensive report encompassing the role of biomarkers in the context of clinical trials that charts the course for future research of new therapies and disease modifying drugs for OA [23,24]. Research focuses in the structural components of extracellular matrix, especially type II collagen degradation markers [25].…”