Department of Biophysics and Physiology, Laboratory of Experimental Cancerology, Federal University of Piauí, 64049-550 Teresina, Brazil.
Department of Biophysics and Physiology, Laboratory of Experimental Cancerology, Federal University of Piauí, 64049-550 Teresina, Brazil.
Pharmacol Res. 2021 Jun;168:105582. doi: 10.1016/j.phrs.2021.105582. Epub 2021 Mar 26.
Chloroquine (CQ) and hydroxychloroquine (HCQ) are the most common drugs used to relieve acute and chronic inflammatory diseases. In this article, we present a review about the use of CQ and HCQ in antitumor therapies based on autophagy mechanisms. These molecules break/discontinue autophagosome-lysosome fusions in initial phases and enhance antiproliferative action of chemotherapeutics. Their sensitizing effects of chemotherapy when used as an adjuvant option in clinical trials against cancer. However, human related-MDR genes are also under risk to develop chemo or radioresistance because cancer cells have ability to throw 4-aminoquinolines out from digestive vacuoles well. Additionally, they also have antitumor mechanism unrelated to autophagy, including cell death from apoptosis and necroptosis and immunomodulatory/anti-inflammatory properties. However, the link between some anticancer mechanisms, clinical efficacy and pharmacological safety has not yet been fully defined.
氯喹（CQ）和羟氯喹（HCQ）是最常用于缓解急性和慢性炎症性疾病的常用药物。在本文中，我们回顾了基于自噬机制的 CQ 和 HCQ 在抗肿瘤治疗中的应用。这些分子在早期阶段破坏/中断自噬体 - 溶酶体融合，并增强化疗药物的抗增殖作用。当它们作为癌症临床试验中的辅助治疗选择时，具有增敏化疗的作用。然而，人类相关的多药耐药基因也有发展化疗或放疗耐药性的风险，因为癌细胞有能力将 4-氨基喹啉从消化液泡中很好地排出。此外，它们还具有与自噬无关的抗肿瘤机制，包括细胞凋亡和坏死性细胞死亡以及免疫调节/抗炎特性。然而，一些抗癌机制、临床疗效和药理安全性之间的联系尚未完全确定。
