Has Drug Repurposing Fulfilled its Promise in Acute Myeloid Leukaemia?

Abstract

Drug repurposing is a method of drug discovery that consists of finding a new therapeutic context for an old drug. Compound identification arises from screening of large libraries of active compounds, through interrogating databases of cell line gene expression response upon treatment or by merging several types of information concerning disease-drug relationships. Although, there is a general consensus on the potential and advantages of this drug discovery modality, at the practical level to-date no non-anti-cancer repurposed compounds have been introduced into standard acute myeloid leukaemia (AML) management, albeit that preclinical validation yielded several candidates. The review presents the state-of-the-art drug repurposing approach in AML and poses the question of what has to be done in order to take a full advantage of it, both at the stage of screening design and later when progressing from the preclinical to the clinical phases of drug development. We argue that improvements are needed to model and read-out systems as well as to screening technologies, but also to more funding and trust in drug repurposing strategies.

Keywords: acute myeloid leukaemia; candidate compounds; drug repurposing.

Figure 1

Candidate compounds to treat acute myeloid leukaemia (AML) obtained through a host of methods tested in preclinical (outer circle) and clinical setting (inner circle).

Figure 2

Candidate compounds to treat AML classified by original therapeutic indication.

Figure 3

Drug discovery is like climbing a mountain. Repurposing partially follows beaten tracks whilst de novo development carves out new paths for itself. So far only agents developed de novo made it to obtaining the FDA approval.