Epigenetic-based therapy: From single- to multi-target approaches

The treatment of cancer has traditionally been based on the identification of a single molecule and/or enzymatic function (target) responsible for a particular phenotype, and therefore on the ability to stimulate, attenuate or inhibit its activity through the use of selective compounds. However, cancer is no longer considered a disease caused by a single factor, but is now recognized as a multi-factorial disorder. Genetic, epigenetic and metabolic factors all contribute to neoplasia, causing significant changes in molecular networks that govern cell growth, development, death and specialization. Consequently, many antitumor therapies are no longer directed against a single target but the biological system as a whole, in which functions determining the onset and maintenance of a physio-pathological state are modulated. The field of epi-drug discovery is currently in a transitional phase where the search for putative anticancer drugs is shifting from single-target-oriented molecules to network-active compounds and to epi-drugs used in combination with other epi-agents and with traditional chemotherapeutics. This review illustrates the pros and cons of each therapeutic option, providing examples in support of single-target and multi (network)-target epi-drug approaches.