A Database of Drug Repurposing Clinical Trials in Oncology.

Abstract

Drug repurposing is a strategy that seeks new medical treatments from existing licensed medications rather than from de novo development of new molecules. The rationale for this approach is predicated in part on the perceived advantages of using existing data on safety and toxicity, the ready availability of such medicines and the potential for lowered drug costs (Pantziarka et al., 2014; Bertolini et al., 2015). In particular, the use of non-cancer drugs as new cancer treatments is becoming an increasingly attractive proposition. While bibliometric data shows an exponential increase in the peer reviewed literature in this area, much of it remains focused on drug candidate identification and pre-clinical studies (Pantziarka et al., 2020). There has been a growth of computational support for candidate identification in recent years, with a focus on algorithms and database support to enhance disease-target-drug analysis (Peyvandipour et al., 2018; Zhu et al., 2018; Tanoli et al., 2021). A notable contribution to the field is the PRISM (profiling relative inhibition simultaneously in mixtures) system from the Broad Institute. This open access resource records the growth inhibitory activity of thousands of compounds against more than 500 cancer cell lines (Corsello et al., 2020). The importance of regulatory approvals, intellectual property rights and other non-clinical factors in repurposing have also been highlighted and discussed, particularly by Verbaanderd et al. (2019) and by Begley et al. (2021). To date there has not been a comprehensive analysis of clinical trials in repurposing in oncology. The answers to key questions regarding the proportion of clinical trials by drug, by phase, by geographic location or cancer indication remain unclear. This work describes the methodology for the creation of a curated database of drug repurposing clinical trials in oncology. The database, which we have called the ReDO_Trials_DB, is available as an online, open access database with basic search, filtering and download functionality. Definitions of drug repurposing, sometimes also called drug repositioning, vary widely and can encompass multiple drug development strategies from the further development of previously shelved compounds to the use of licensed cancer drugs in new cancer types to the exploration of non-cancer drugs as new cancer therapeutics (Pushpakom et al., 2019; Pantziarka et al., 2020). In this work we are focused specifically on the use of licensed non-cancer drugs as potential cancer therapeutics. To this end the list of drugs classed as repurposing candidates is derived from the ReDO_DB (https://www.anticancerfund.org/en/redo-db), our previously published drug repurposing database (Pantziarka et al., 2018). To recap, drugs are included in the ReDO_DB if they meet the following criteria: • Licensed by one or more national/international medicines regulatory agency (e.g., FDA, EMA, MHRA etc) • Are not licensed for a cancer indication, although drugs used for symptomatic or diagnostic uses in cancer can be included (e.g., anti-emetics) if there is evidence of anticancer activity as well • Have published evidence of anti-cancer activity, including in vitro, in vivo, case reports, observational studies or clinical trials In this paper we present the ReDO_Trials_DB, the methodology employed to generate and maintain it and a first description of the number and characteristics of the included trials.