In Silico Oncology Drug Repositioning and Polypharmacology

Abstract

Network-aided in silico approaches have been widely used for prediction of drug-target interactions and evaluation of drug safety to increase the clinical efficiency and productivity during drug discovery and development. Here we review the advances and new progress in this field and summarize the translational applications of several new network-aided in silico approaches we developed recently. In addition, we describe the detailed protocols for a network-aided drug repositioning infrastructure for identification of new targets for old drugs, failed drugs in clinical trials, and new chemical entities. These state-of-the-art network-aided in silico approaches have been used for the discovery and development of broad-acting and targeted clinical therapies for various complex diseases, in particular for oncology drug repositioning. In this chapter, the described network-aided in silico protocols are appropriate for target-centric drug repositioning to various complex diseases, but expertise is still necessary to perform the specific oncology projects based on the cancer targets of interest.

Keywords: Cancer genomics; Drug repositioning; Drug-target interactions; Network-based inference; Panomics; Polypharmacology; Precision oncology; Systems biology; Systems pharmacology; Targeted therapy.