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Complex diseases require complex therapies

Ravi Iyengar

Author Affiliations

  • Ravi Iyengar, 1 Department of Pharmacology and Systems Therapeutics, Systems Biology Centre New York, Icahn School of Medicine, New York, New York, USA

Since the rise of modern pharmaceutical research and industry in the 1950s, drugs have been used to treat an increasingly wide range of diseases. From antibiotics for treating infections, to antivirals to treat HIV/AIDS, to drugs for hypertension and cancer, drug‐based therapies have had enormous effects in curing or converting often fatal diseases into manageable conditions. Even pathophysiologies, such as peptic ulcers, that once required surgery are now routinely treated by drugs.

Along with the many successes, several limitations have also become evident. Many diseases, especially those that progress in severity, remain difficult to treat with drugs. The list of such disorders is long and includes aneurysms, congestive heart failure, diabetes, kidney disease and many types of cancer. Even drugs that are efficacious do not work for everybody. Effective drugs cause serious adverse events in a subset of users. As we often cannot predict who might suffer from these side effects, the drug is typically taken off the market.

These problems have generated a sense that our current approaches might have reached their limits and that we need new thinking to drive both drug discovery and usage. The extensive advances in our understanding of the basic molecular and cell biology of humans, other mammalian organisms and model organisms indicate that there are probably many more cellular components that could be targeted by drugs to fight disease. Another general insight is that cellular components interact with one another to form extensive networks. These networks have the capability to regulate and coordinate a range of subcellular functions, which gives rise to cellular phenotypes [1,2]. These cellular phenotypes underlie the tissue and organ functions that are characteristics of both health and disease.

Malfunctions at the molecular level, when propagated to a higher level of organization, give rise to disease …

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