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 anticancer therapy.
Objective: This article reviews the molecular mechanisms, clinical evaluation and recent patents of
CQ analogs in cancer therapy.
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.