Background: Drug repurposing is emerging as an attractive strategy with lower attrition rate, lower cost and
shorter timeframe than traditional drug discovery methods. Chloroquine (CQ) and its analogs are old drugs originally
indicated for malaria treatment. Serendipitous discovery in early years revealed its anti-inflammatory properties, thus
allowing its repositioned use in autoimmune diseases. Recent evidence also suggested its potential therapeutic use for
Objective: This article reviews the molecular mechanisms, clinical evaluation and recent patents of CQ analogs in cancer
Methods: Literature and patent searches were conducted using PubMed database and Google Patent/USPTO Patent
Search database, respectively. The keywords including “chloroquine”, “hydroxychloroquine”, “chloroquine analogs”,
“chloroquine derivatives”, “repurposing”, “autophagy”, and “cancer” were used.
Results: CQ analogs have been reported to elicit their anticancer effects by modulating autophagy, inducing apoptosis,
eliminating cancer stem cells, normalizing tumor vasculature and modulating antitumor immunity. As documented by
recent patents and clinical trials, CQ analogs have been repurposed as an adjuvant therapy and combined with other
anticancer agents for synergistic enhancement of treatment efficacy. However, most clinical trials on CQ only
demonstrated modest improvement in anti-cancer efficacy.
Conclusion: Given that CQ loses its anticancer activity in acidic and hypoxic environment within a tumor, novel CQ
analogs and/or their formulations are under active investigation to improve their physicochemical properties and
biological activity. On the other hand, identification of new biomarkers for better patient selection has been advocated in
future trials in order to realize the repurposing of CQ analogs for cancer treatment in a personalized manner.