Approaching Complex Diseases

Aimed at pharmacologists, systems biologists, and historians and philosophers of medicine, this book examines where pharmacology research could head next. It thoroughly tests the assumptions behind a proposed major change in how the field thinks about drugs.

Drug developers have struggled to produce new medicines. When the industry adopted a target-based approach in the 1990s, many researchers welcomed it. Twenty years on, that model has not improved discovery or efficiency. Many chosen targets could not be drugged, or had weak links to the diseases they were meant to treat, so the resulting drugs were either too toxic or not effective enough.

Research in systems biology points to phenotypic robustness and network structure, which suggests that highly selective compounds may deliver less clinical benefit than drugs that act on several targets at once. The authors argue that this recognition of polypharmacology bears directly on the two main causes of failure in drug development, lack of efficacy and toxicity. Combining network biology with polypharmacology could widen the range of targets that can realistically be drugged.