Despite these examples, it was generally anticipated 10 years ago that progress in translational and personalized medicine would be more advanced than it is today. Particularly, it was anticipated that rather than curing diseased patients healthy people would be kept healthy.
Particularly, because of the globalization of society the scope of this functional network has changed from local to global in nature. Distance is no longer a key factor in selecting external expertise to support a project; now it is the quality, speed and costs of external partners. Today, many scientists have developed global connections and routinely send samples across continents for analysis. In addition, the marketplace has also globalized. Whereas earlier most, if not all of the commercial and research focus of pharmaceutical and diagnostic industries was on Western markets in Europe and the U.S., it has recently shifted to the emerging markets, mainly, Brazil, Russia, India and China.
Summary (Continued)
However, distinct differences have not only been found in the response to drugs originally developed for the Western markets but also in the path physiology and clinical features of diseases. Without doubt, the different genetic backgrounds, dietary preferences and lifestyles of populations across the globe contribute to this, but clearly more research is needed to investigate this. Supported by their increased economic power, the emerging countries currently invest heavily in biomarker research, aiming to improve existing therapeutic treatments and generate more personalized drugs for their markets.
There have also been compelling trends regarding the nature of the biomarkers themselves. In conjunction with identifying more candidate biomarkers, there is an increased desire to valorize biomarkers and develop them from basic research tools into robust diagnostic tests that can be applied for clinical decision-making.
Translational medicine needs such validated biomarkers, as only then can equivalency of biological responses across models and humans be proven. Recent research has yielded many translational biomarkers (DNA, RNA, protein, metabolite and imaging) in different stages of validation that are being applied to provide data supporting translational and personalized medicine. Another interesting trend is to combine quantitative biomarker data and clinical readouts to provide a more detailed characterization of a disease state. This enables clinicians not only to diagnose diseases but also to specify the subtype or causal origin of the path physiology, potentially leading to a more tailored treatment.
In the biomarker discovery space, new data-rich biomarker discovery technologies have emerged that are dramatically changing our knowledge of preclinical and human systems, information that is imperative to enable translational and personalized medicine. Particularly, next-generation sequencing, whereby variants and regulation of DNA and RNA on nucleotide level are revealed and mass spectrometry, whereby peptide, protein and metabolite is forms are monitored to reflect acute perturbations of biological systems, have yielded a wealth of observations on variants in healthy and diseased states. This progress has dramatically changed the landscape of biomarker discovery and development, and strongly increased the potential of biomarkers for use in human medicine.
CHALLENGES
Despite the progress that has been made, several basic elements are not yet in place to permit biomarkers to reach their full potential in human medicine. First and foremost, there are still insufficient accepted robust biomarker tests that can be applied in the clinic. Human diseases are largely complex in nature and require several biomarkers to mechanistically describe the imbalance in the metabolic equilibrium responsible for the disease and the effect of treatment.
The number of published biomarkers with clear biological relevance needs to increase but, even more importantly, the clinical validation of such biomarkers needs to improve greatly.
Without extensive validation, the outcome of a biomarker test cannot be used in important clinical decisions as done in personalized medicine. Clinical biomarker validation should optimally be performed by applying standardized procedures and protocols to test independent clinical samples across multiple independent laboratories. However, in reality, this is rarely carried out.
The commitment of biomarker researchers to engage in long lasting and expensive biomarker validation projects is limited, partly due to the pressure to publish innovative findings in high impact journals and secure funding. Although clinical validation of biomarkers, including the development of quantitative biomarker assays with high accuracy, specificity and reproducibility, is essential to enabling translational and personalized medicine, it has limited news value and as such is less likely to be published. In addition, despite constructive efforts by regional activity, there is a lack globally of (pre)clinical samples that are highly characterized, are properly stored, have associated phonotypical metadata and are being made available for multicenter biomarker validation.
As a result, researchers focus on objectives that are considered more innovative and achievable in the short term, which only rarely include reporting of robust clinical biomarker validation. A challenge in biomarker discovery is how to exploit the great potential of novel high-content technologies as mentioned above. Data analysis methods are still being optimized and knowledge on the biological interpretation of the newly identified variants is scarce. Moreover, there is often insufficient knowledge on variation in the biomarkers themselves across the various population groups in the world.
OPPORTUNITIES
Embracing an optimistic view, each challenge is an opportunity for progress. The key to progress is funding, which is strongly increasing for translational medicine globally. This, together with the downsizing of internal biomarker activities in larger companies, has considerably stimulated new economic business opportunities. Many specialized spin-off companies have been formed, which together with contract research organizations, vendors and central laboratories, are working together with larger companies and universities to drive pharmaceutical and diagnostic biomarker development. Importantly, this functional network now also includes the emerging markets and their populations, driving biomarker research across the globe.
Another opportunity lies in the nature of the funding of translational medicine. Funding agencies prefer to support multicenter consortia in public-private partnerships rather than single laboratories, bringing together basic and applied biomarker researchers and stimulating knowledge transfer and a focus toward applied biomarker research. Such collaborations have shown to lead to increased awareness of the value of cross-discipline biomarker research, improved data analysis workflow, and increased identification and development of biomarkers for specific diseases and mechanisms. In addition, there is now the opportunity to functionally link multiple independent biorepositories across the globe through global networks to share access to unique clinical samples.
Together, these initiatives will make robust biomarker assays and clinical samples available to a larger group of testing laboratories, thus increasing the quality of published validated biomarkers and their application in translational and personalized medicine. Ultimately, this higher level of biomarker knowledge and tools will result in the transformation of disease management into health management. At present, it may seem a utopia but with the impressive progress seen in recent years, it may be sooner than expected.