Molecular Mechanisms of Chloroquine and Hydroxychloroquine Used in Cancer Therapy


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Abstract

Tumour relapse, chemotherapy resistance, and metastasis continue to be unsolved issues in cancer therapy. A recent approach has been to scrutinise drugs used in the clinic for other illnesses and modify their structure to increase selectivity to cancer cells. Chloroquine (CQ) and hydroxychloroquine (HCQ), known antimalarials, have successfully treated autoimmune and neoplastic diseases. CQ and HCQ, well-known lysosomotropic agents, induce apoptosis, downregulate autophagy, and modify the tumour microenvironment. Moreover, they affect the Toll 9/NF-κB receptor pathway, activate stress response pathways, enhance p53 activity and CXCR4-CXCL12 expression in cancer cells, which would help explain their effects in cancer treatment. These compounds can normalise the tumourassociated vasculature, promote the activation of the immune system, change the phenotype of tumour-associated macrophages (from M2 to M1), and stimulate cancer-associated fibroblasts. We aim to review the historical aspects of CQ and its derivatives and the most relevant mechanisms that support the therapeutic use of CQ and HCQ for the treatment of cancer.

About the authors

Juan De Sanctis

Faculty of Medicine and Dentistry,, Institute of Molecular and Translational Medicine

Email: info@benthamscience.net

Jaime Charris

Organic Synthesis Laboratory, Faculty of Pharmacy, Central University of Venezuela

Email: info@benthamscience.net

Zuleyma Blanco

Organic Synthesis Laboratory, Faculty of Pharmacy,, Central University of Venezuela

Email: info@benthamscience.net

Hegira Ramírez

Faculty of Health Sciences and Human Development, Research Directorate,, Center for Sustainable Development Studies, ECOTEC University

Email: info@benthamscience.net

Gricelis Martínez

Faculty of Medicine, Institute of Immunology,, Central University of Venezuela

Email: info@benthamscience.net

Michael Mijares

Faculty of Medicine, Institute of Immunology,, , Central University of Venezuela,

Author for correspondence.
Email: info@benthamscience.net

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