Fig. 1

Evolution of Drug Development. We may distinguish 5 distinct phases in the evolution of drug discovery. In the first half of the last century, that was mainly occurring by serendipity (phase 1); nonetheless important drugs were identified, including Aspirin by Hoffman and penicillin by Fleming. In the second part of the last century (phase 2), the development of massive chemical libraries that could be tested in vivo in mice, subsequently translated into selective human groups, has allowed the definition of thousands new drugs that have revolutionized medicine, especially cancer therapy. In this century, we are equipped with the sequence of the entire human genome and large numbers of genetic banks, with specific mutations, deletions, polymorphisms and histone modifications (phase 3). This permitted the identification of intelligent drugs, acting only on one single target and therefore wanton toxicity (phase 4), in other wards, selecting the specific drug for the individual patient. With metabolic mutation, identification of predisposing mutations, selection of monitoring or predictive cluster of genes, proteins or phospho-protein, oncology will enter the 4P medicine: Preventive, Personalized, Predictive, Participative