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Ecancermedicalscience. 2017 Nov 23;11:781. doi: 10.3332/ecancer.2017.781. eCollection 2017.

Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents.

Author information

1
Anticancer Fund, Brussels, 1853 Strombeek-Bever, Belgium.
2
Cell Death Research and Therapy Lab, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
3
Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
4
GlobalCures, Inc, Newton, MA 02459, USA.
5
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Current address: Emory School of Medicine, Atlanta, GA 30322, USA.
6
The George Pantziarka TP53 Trust, London KT1 2JP, UK.

Abstract

Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. Thus far, clinical results are mostly in favour of the repurposing of CQ. However, over 30 clinical studies are still evaluating the activity of both CQ and HCQ in different cancer types and in combination with various standard treatments. Interestingly, CQ and HCQ exert effects both on cancer cells and on the tumour microenvironment. In addition to inhibition of the autophagic flux, which is the most studied anti-cancer effect of CQ and HCQ, these drugs affect the Toll-like receptor 9, p53 and CXCR4-CXCL12 pathway in cancer cells. In the tumour stroma, CQ was shown to affect the tumour vasculature, cancer-associated fibroblasts and the immune system. The evidence reviewed in this paper indicates that both CQ and HCQ deserve further clinical investigations in several cancer types. Special attention about the drug (CQ versus HCQ), the dose and the schedule of administration should be taken in the design of new trials.

KEYWORDS:

Repurposing Drugs in Oncology (ReDO) project; anti-malarial agents; antineoplastic agents; chloroquine (CQ); drug repositioning; hydroxychloroquine (HCQ); neoplasms

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