Repurposing fluoroquinolones as cancer chemosensitizers: a way to overcome cancer therapeutic bottleneck.

Drug repurposing (DR) is a strategy to develop novel drugs from pre-approved drugs. To overcome the limitations of conventional drug development pathways, DR is a novel method that is cost-effective, with minimal side effects, and less time-consuming. Contrary to de novo drug discovery, DR eliminates the need for FDA approval. Fluoroquinolones (FQs) are potentially antibiotics, but recently, it has been discovered that FQs are a potential "treasure trove" to circumvent cancer drug resistance. Various in vitro studies on FQs showed their anticancer functionality against various cancer cell lines. Moreover, FQs are found to enhance the therapeutic efficacy of various clinical drugs by acting synergistically or additively in combination therapy. FQs such as ciprofloxacin, moxifloxacin, and levofloxacin are found to enhance the anti-tumor effect of a wide range of FDA-approved chemotherapeutics through multiple mechanisms including cell cycle arrest, apoptosis induction, anti-proliferation, and modulation of EMT. This review will comprehensively focus on the chemosensitization mechanism and cellular targets of FQs. This study provides a scientific basis to explore FQs as potential chemotherapeutic agents for combinational therapy to tackle the current scenario of drug resistance.