Drugging the undruggable proteins in cancer: A systems biology approach

Abstract

In recent years, the research community has, with comprehensive systems biology approaches and related technologies, gained insight into the vast complexity of numerous cancers. These approaches allow an in-depth exploration that cannot be achieved solely using conventional low-throughput methods, which do not closely mimic the natural cellular environment. In this review, we discuss recent integrative multiple omics approaches for understanding and modulating previously identified 'undruggable' targets such as members of the RAS family, MYC, TP53, and various E3 ligases and deubiquitinases. We describe how these technologies have revolutionized drug discovery by overcoming an array of biological and technological challenges and how, in the future, they will be pivotal in assessing cancer states in individual patients, allowing for the prediction and application of personalized disease treatments.

Keywords: Cancer research; Difficult-to-drug proteome; Drug discovery; E3 ligases and deubiquitinases; High-throughput; MYC; Omics; Precision medicine; RAS; Systems Biology; TP53; Undruggable oncogenes.