Medicine is evolving on the whole and the last decade has witnessed steady advances in literally all areas of disease management. One of these is personalized medicine and personalized nutrition. The former, personalized medicine (PM) is a new way of dealing with individual health, using a “personalized” approached sustained by high through-put technologies including pharmacogenetics, pharmacogenomics and epigenetics that are now interlinked with genomic medicine. Individuals have variations in the composition of their genetic characteristics that will affect the availability of functional proteins that will impact functional homeostasis and the outcome of drug therapy. The identification and validation of accurate biomarkers of individual responses to drug or biologic treatment remain prerequisite conditions ascribed to the development of PM and other evolving therapeutic strategies. Targeted therapies have been instrumental to the development of biomarkers to optimise drug development and clinical use. Biomarker validation entails a systematic evaluation to ensure its reliability and is guided by established principles of bio-analytical method validation. The NIH generically defines biomarkers as “characteristics that can be objectively measured as indicators of a biological or pathological process or pharmacological response to a therapeutic intervention” qualifying them to be potentially used across the whole translational medical research process. Biomarkers are therefore touted as the next frontier in the realm of modern medicine as they would represent the essentials in guiding treatment decisions that could enable complementary matching of specific drugs with individual patients, effective patient therapeutic dose and management of drug-related risks. However their intended use should be well defined: diagnostic, prognostic, predictive? This would warrant a clear statement on the goals and population targeted. There has been some success in the identification and development of diagnostic, prognostic and to varying degrees toxicity and pharmacological biomarkers. However little progress is reported for clinically useful predictive markers, for instance in cancer therapy, and they remain potentially the most important in clinical decision-making. A review by Alymani et al (European Journal of Cancer, 46, 869-879, 2010) discusses the recent progress in this area focusing on the key stages in the biomarker development process which comprise discovery, validation, qualification and implementation. Concentrating on predictive markers for selecting systemic therapies for individual patients, this review emphasises the advances and progress in each of these stages in biomarker development and indicate that there is significant motivation to improve the biomarker development process. The authors proposals on the formulation of robust clinical biomarker development methodology with defined processes and acceptance criteria and the appearance of guidance in the form of “roadmaps” from national and multinational review groups for biomarker development seem to be realistic and practical initiatives for the establishment of a strong and acceptable methodology for predictive biomarker development from discovery to clinical implementation.
Both conventional and functional foods have, in the context of structured scientific research process using proteomics, nutragenomics, metabolomics, bioinformatics and genetic susceptibility, extensively contributed to another area of biomarker research which is nutritional biomarker research. In a pertinent review by Verhagen et al, (Mutation Research, 551, 65-78, 2004) the authors emphasize that the future of functional foods will heavily rely on proven efficacy in well-controlled intervention studies with human volunteers. To achieve maximum output of human trials, improvements are needed with respect to study design and optimization of study protocols. Efficacy at realistic intake levels needs to be established in studies with humans via the use of suitable biomarkers, unless the endpoint can be measured directly. The human body is able to deal with chemical entities irrespective of their origin, and the pharmaceutical terms “absorption, distribution, metabolism and excretion” have their equivalent when biomarkers are concerned. A valid point highlighted by the authors and which warrants extensive attention in the light of contradictory data generated from functional food based clinical studies for the past years is the concept of “biomarker kinetics”. Broadly speaking this comprises “formation, distribution, metabolism and excretion”. However, this is at present neither an established science nor common practice in nutrition research on functional foods. The authors rightly point out that sampling times and matrices, for example, are chosen on the basis of historical practice and convenience (for volunteers and scientists) but not on the basis of in depth insight. This may be one of the key factors that could bring in the element of consistency, so much lacking in clinical studies.
The field of biomarker research is exciting and evolving at a fast pace. The momentum presented by the emerging interest of the role of biomarkers in the product lifecycle of drugs (from development to utilization) will continue to provide research and development opportunities for the drug manufacturers, regulatory agencies, academia, biotech organizations and research scientists globally A special issue of the journal Toxicology on the future of biomarkers (Aruoma and Bahorun (2010) Toxicology 278(2)) addresses the emerging concepts and is highly recommended to the reader.
Professor Theeshan Bahorun
Deputy Editor in Chief
Email: tbahorun@uom.ac.mu