Multi-target directed ligands for the treatment of cancer

Cancer remains a major cause of mortality. However, significant progress has been made in understanding the molecular basis of the disease. Cancer is a multigenic and multicellular disease characterized by a multifactorial etiology, which initiates uncontrolled cell growth. The major problem associated with current cancer treatment regimens is ascribable to the development of resistance to therapy, which may arise due to several reasons, such as the overexpression of anti-apoptotic proteins, mutations in key signaling molecules, overexpression of drug efflux pumps, or the presence of dormant and/or resistant tumor cells. Most of the anticancer drugs in clinical use are based on the principle of ‘one molecule - one target - one malady’. However, multifactorial diseases such as cancer may greatly benefit from therapies simultaneously hitting multiple key pathways and/or their pathogenic cross-talk. The design strategy for multi-target-directed ligands (MTDLs) involves the incorporation of two or more distinct pharmacophores of different drugs in a single structure to develop hybrid molecules. MTDLs can bind/inhibit two or more targets simultaneously, thus boosting the compound’s therapeutic potential via a polypharmacological approach. In addition, these also eliminate the chances of development of drug resistance frequently observed in case of single targeted regimens. Modern drug discovery has the power to identify potential multifunctional modulators for biologically and clinically validated targets among millions of compounds. The design of MTDLs is an essential and promising research area since recent research confirmed the potential therapeutic benefit for managing/treating complex multifactorial diseases. Despite the significant amount of drug discoveries in the vast field of cancer therapy, there is still an urgent need for novel and innovative treatments. The MTDL approach holds great potential in cancer therapy since it may significantly simplify treatment regimens with respect to standard combination therapy, reduce the risk of possible drug-drug interactions, and most importantly, limit the insurgence of resistance. In the present Research Topic, several multitargeted approaches to cancer therapy are showcased in original articles and discussed from an interdisciplinary point of view, thus providing an updated picture of the latest progress in the field.