Repurposing Chloroquine Analogs as an Adjuvant Cancer Therapy

重新调整用途 氯喹 药物重新定位 医学 羟基氯喹 临床试验 癌症 自噬 药品 药理学 辅助治疗 佐剂 疟疾 肿瘤科 细胞凋亡 内科学 免疫学 化学 生物 疾病 2019年冠状病毒病(COVID-19) 传染病(医学专业) 生物化学 生态学
作者
Winnie Fong,Kenneth K.W. To
出处
期刊:Recent Patents on Anti-cancer Drug Discovery [Bentham Science Publishers]
卷期号:16 (2): 204-221 被引量:14
标识
DOI:10.2174/1574892815666210106111012
摘要

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.
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