Abstract
 

The end of medicine as we know it: From Chronic Disease to Mechanism-Based Cure

For complex diseases, most drugs are highly ineffective, and the success rate of drug discovery is in a constant decline. Whilst low quality, reproducibility issues, and translational irrelevance of most basic and preclinical research have contributed to this, the current organ-centricity of medicine and the one disease-one target-one drug dogma obstruct innovation most profoundly. Systems and network medicine and their therapeutic arm, network pharmacology, revolutionize how we define, diagnose, treat and ideally cure diseases. Descriptive disease phenotypes are replaced by endotypes defined by causal, multi-target signaling modules that also explain respective comorbidities. These modules are however distinct from classical pathways, which we now recognize to be not more than highly curated mind maps of signaling events. Modules more often than not contain several fragments of several different canonical pathways. Precise and effective therapeutic intervention depends on precise inclusion and exclusion of module members and is subsequently achieved by synergistic multi-compound network pharmacology, ideally through drug repurposing, obviating the need for drug discovery, and speeding up the clinical translation. Network pharmacology is, however, not to be confused with current combination therapies with multiple non-synergistic drugs targeting non-causal proteins that rather treat symptoms but do not cure disease.