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The Future Of Drug Development: The Paradigm Shift Towards Systems Therapeutics

The Paradigm Shift Towards Systems Therapeutics

Progress in cell biology, genetics, molecular, and systems pharmacology is the driving force behind a current paradigm shift in drug research. This paradigm shift shapes new avenues for advanced treatments that are commonly referred to as 'systems therapeutics'. Systems therapeutics differ in many ways from current drugs because they target biological networks rather than single transduction pathways, and affect disease processes rather than physiological processes. Here, we examine how the paradigm shift towards systems therapeutics will change current scientific concepts of the interactions between drugs and diseases, the organization of research and development, as well as the clinical use and therapeutic evaluations of therapeutic interventions.

Where do we come from?
For centuries, the discovery and application of medicine has been driven by myriad clinical experiences, serendipity, and empirical trial and error, with, in the early days, many therapies being isolated from natural sources. Our current therapeutic arsenal still includes many products with an origin or an initial lead in nature (e.g., paclitaxel, statins, and antimicrobial agents) and revisiting natural products for drug discovery remains actively pursued.

During the second half of the 20th century, progress in science (e.g., increase in synthetic organic chemistry or the development of pharmacology-based concepts of drug action) marked a 'paradigm shift' in drug research. Adoption of the 'single path transduction model', describing drug effects as the result of interactions of a single drug at a single receptor, led to ground-breaking drugs, such as propranolol or cimetidine. In practice, these drugs are typically applied in fixed doses according to a 'one size fits many' principle, with a major emphasis on the control of symptoms of the disease. These single receptor-based drugs, together with anti-infectives, such as penicillin or streptomycin, resulted in unprecedented progress in drug development during the decades after World War II.

However, in recent years, the development of new drugs on the basis of the 'single target-single drug' concept stagnated, with significantly reduced success rates and prolonged development times. The stagnation in drug development also coincides with major challenges in healthcare systems worldwide. Among many factors, aging of the population has led to a significantly increased burden of disease, with seemingly infinite demands for healthcare resources, both operationally, capacity wise, and budgetary 5, 6. However, apart from demographic changes, many transformations in current healthcare systems (e.g., increased patient focus, demand for equal access, proportionate regulation, and globalization) also affect the space of drug research, the business model for the industry, and the socioeconomic dimensions of pharmacotherapy.

Now, more than a decade into the 21st century, through progress in cell biology, genetics, molecular, and systems pharmacology, the next paradigm shift in drug research is unfolding. The adoption of 'biological network transduction models', evaluating drug effects as the result of multiple interactions in a biological network, has yielded unprecedented opportunities to understand the functioning of biological systems, to identify the molecular mechanisms of drug action, and to design therapeutic strategies aimed at modifying disease processes rather than controlling symptoms.

It is expected that these transitions in science and drug development will shape new avenues for an avalanche of advanced treatments reaching patients in the years to come. Conceptually, these therapeutic interventions differ in many ways from current drug treatments and are commonly referred to as 'systems therapeutics'.

Under the title 'Future Medicines For One World', the 6th FIP Pharmaceutical Sciences World Congress (PSWC) in Stockholm on May 20-24, 2017 addressed the question of how to make systems therapeutics a reality. The views presented in this paper are inspired by the PSWC 2017. First, we introduce the scientific principles of systems therapeutics. Next, we discuss how the paradigm shift towards systems therapeutics might change current scientific concepts of the interactions between drugs and disease, the organization of research & development (R&D), as well as the clinical use and therapeutic evaluation of systems therapeutic interventions. We conclude with a discussion of the impact of the systems approach on pharmaceutical sciences as a scientific discipline.



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