Comprehensive targeting: the avenue to a personalized, highly effective, innocuous, and cost-effective medicine of the future

Targeting individuals instead of averaged cohorts

We need to learn how to integrate genetic setup, molecular presentation, and clinical variables with randomized trial information in a way that patient selection, drug selection, drug dose, drug duration result in an optimal individual benefit, the lowest individual side effect profile is achieved. Only such a personalized approach, based on molecular information has the chance of improving both, quality AND cost effectiveness of today’s medicine in parallel.

Targeting therapies to the right organs, cells, and receptors, and pathways

In the past decades, biotechnology, systems biology and nanomedicine have developed on separate tracks, but it is increasingly evident that their combination will be of particular benefit to clinical medicine:

• Medical biotechnology, definable as the use of biomacromolecules, cells, and biological processes for a medical purpose, has been successfully applied in a number of medical challenges, visible in the successful clinical introduction of insulin, growth factors, antibody therapies (and certain cell therapies). In a typical scenario, a specific ligand/target receptor interaction is inhibited by a monoclonal antibody to achieve a desired therapeutic effect, an application usually termed “targeted therapy”, in particular when used in cancer therapy. The term “targeted therapy” is also used for inhibition of such tumor-specific pathways by small molecular inhibitors.

• Nanomedicine has been based on insights on supramolecular chemistry, molecular biology, physics and material sciences. It has developed the capability of designing complex nanosize, supramolecular objects composed from a broad range of materials including polymers, metals, lipids, biomacromolecules and small drug molecules. This allows the design of multifunctional nano-objects with separation of concerns like receptor docking and biologic effect on the target, a strategy for which the term “targeted delivery” is typically used. Beyond the basic concept of such delivery, a major interest in nanomedical approaches is the possibility to embed complex functionality, like biosensors and triggered functionalities, into this nano-object.

Targeting: complementary value of nanomedical and biotechnological approach

The greatest potential of those apparently separate fields is, however, in their interaction: For example, peptides and antibodies are excellent ligand molecules on nanocarriers built from synthetic materials: nanocarriers permit a much higher “payload per ligand ratio” compared to antibody drug conjugates. Conversely, nanomedical carrier technologies appear to be the enabler for future breakthroughs in biotechnology like the targeted use of nucleic acid silencing technologies (RNA inhibition) in clinical application.

Medical targeting of the future based on systems biology of disease and individuals

Medical targeting of the future will combine disease- and patient-specific genomics and gene expression analysis, make use of systems biology approaches to integrate this information into a disease model at the level of the target cell, will choose or assemble suitable multifunctional carrier/payload combinations and will exploit theragnostic capabilities of nanomedical objects for therapy and disease monitoring in combination.

For medical biotechnology as well as for nanomedicine, understanding specific diseases in specific individuals based on a systems approach, including elucidation of suitable cellular targets that yield therapies with optimum benefit, minimum side effect and translate into improved cost efficacy of medicine are the way to advance together.

Such a medicine of the future will overcome the simplistic “evidence-based” one-fits-all approach and replace it by a comprehensive “knowledge-based” medicine that puts the individual again in the center, delivering individually tailored therapies that are powerful, innocuous and cost-effective.