Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment

Abstract

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of tumors of different origin to increase the efficacy of cytotoxic agents. Such a strategy can be effective in overcoming the resistance of cancer cells to standard chemotherapy or anti-angiogenic therapy. This review presents the results of the combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells, animal xenografts models, and in a few clinical trials. The effects of such an approach on the viability of cancer cells or tumor growth, as well as autophagy-dependent and -independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ, are summarized. Although the majority of experimental in vitro and in vivo studies have shown that CQ/HCQ can effectively sensitize cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Nevertheless, the pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, and the development of more specific inhibitors is required.

Exploring Importance and Regulation of Autophagy in Cancer Stem Cells and Stem Cell-Based Therapies

“…In addition to typical cancer treatments, chloroquine and hydroxychloroquine have been explored to render CSCs more sensitive to cell death. [153] Genetic Interventions Genetic therapies targeting autophagy regulators including ATG genes and mTOR signaling have demonstrated promising results in preclinical cancer models. [154] Regenerative Medicine…”

Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy

“…Cisplatin is widely used as one of the most effective chemotherapeutic agents for the treatment of cancers 130 and has been shown to increase apoptosis in human lung cancer cells (A549 and H460) and epithelial ovarian cancer cells (SKOV3 and hey) when combined with CQ, via autophagy inhibition. 16 , 131 Chen et al revealed that pterostilbene combined with CQ significantly improved autophagy inhibition, decreased cell viability and increased apoptosis in pancreatic ductal adenocarcinoma cells via the downregulation of the RAGE/STAT3 and AKT/mTOR pathways. 17 Moreover, Monma et al found CQ could enhance TRAIL-induced apoptosis in two human pancreatic cancer cell lines: MiaPaCa-2 and Panc-1.…”