Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Pfab, Christina; Schnobrich, Luisa; Eldnasoury, Samir; Gessner, André; El-Najjar, Nahed

SIMPLE SUMMARY: Despite the leaps and bounds in the prevention and treatment of cancer, it remains the second leading cause of death worldwide. A significant hurdle during cancer treatment is the occurrence of intrinsic and acquired therapeutic resistance. This latter case emphasizes the need for new drugs to overcome the challenges resulting from the current therapy. Considering that every drug has at least six off-targets, which might be relevant in cancer therapy, makes drug repurposing an excellent mean to speed up access to new therapeutic options. This review aims to thoroughly discuss anti-microbial agents currently in different trials or those evaluated in pre-clinical settings against various types of cancer and provide an overview of the mechanism(s) by which these agents exert their effects. ABSTRACT: The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.