Multiple Ligand Strategy in anticancer drug discovery

In recent years, the advent of the targeted therapy has significantly contributed to the increased success rate of cancer chemotherapy, and compounds able to inhibit a single target protein in order to selectively kill neoplastic cells have been actively searched. However, it soon emerged that some of the most effective agents owed their action to the ability to target several proteins simultaneously thus obtaining a synergistic effect on different pathways involved in the neoplastic development. As a consequence of that, also in the field of anticancer drug discovery, the Multiple Ligand Strategy has started to receive the attention that it had already gained in other therapeutic fields, like that of neurodegenerative diseases. This chapter is mainly focused on the paradigm shift that is ongoing in anticancer drug research from single-targeted compounds to multi-targeted agents, and in particular on the design strategies that are guiding the search of novel lead compounds. The presentation of the issue also includes some considerations on the use of in silico methods for assisting the identification of new multi-target compounds, and is illustrated by the discussion of some selected case histories.