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Chloroquine in cancer therapy: a double-edged sword of autophagy.

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TLDR
The functions of autophagy in cancer and kidney injury are summarized, especially focusing on the use of chloroquine to treat cancer, and the possible side effects are addressed in the combined use ofchloroquine and anticancer drugs.
Abstract
Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the other hand, however, the kidneys are highly vulnerable to chemotherapeutic agents. Recent studies have shown that autophagy plays a protective role against acute kidney injury, including cisplatin-induced kidney injury, and thus, we suspect that the use of chloroquine in combination with anticancer drugs may exacerbate kidney damage. Moreover, organs in which autophagy also plays a homeostatic role, such as the neurons, liver, hematopoietic stem cells, and heart, may be sensitive to the combined use of chloroquine and anticancer drugs. Here, we summarize the functions of autophagy in cancer and kidney injury, especially focusing on the use of chloroquine to treat cancer, and address the possible side effects in the combined use of chloroquine and anticancer drugs.

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Citations
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Journal ArticleDOI

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Daniel J. Klionsky, +2522 more
- 21 Jan 2016 - 
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Journal ArticleDOI

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Daniel J. Klionsky, +2983 more
- 08 Feb 2021 - 
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
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Cancer metabolism: a therapeutic perspective

TL;DR: How cancer cells reprogramme their metabolism and that of other cells within the tumour microenvironment in order to survive and propagate, thus driving disease progression is discussed; in particular, potential metabolic vulnerabilities that might be targeted therapeutically are highlighted.
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Disrupting proton dynamics and energy metabolism for cancer therapy

TL;DR: This Review presents the key pH-regulating systems and synthesizes recent advances in strategies that combine the disruption of pH control with bioenergetic mechanisms and discusses the possibility of exploiting, in rapidly growing tumours, acute cell death by 'metabolic catastrophe'.
References
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Journal ArticleDOI

Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies

TL;DR: Examination of tumor-bearing animals and identification of novel renoprotective strategies that do not diminish the anticancer efficacy of cisplatin are essential to the development of clinically applicable interventions.
Journal ArticleDOI

The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.

TL;DR: Results indicate that constitutive autophagy in the heart under baseline conditions is a homeostatic mechanism for maintaining cardiomyocyte size and global cardiac structure and function, and that upregulation of autophagic in failing hearts is an adaptive response for protecting cells from hemodynamic stress.
Journal ArticleDOI

Autophagy-deficient mice develop multiple liver tumors

TL;DR: The results suggest that autophagy is important for the suppression of spontaneous tumorigenesis through a cell-intrinsic mechanism, particularly in the liver, and that p62 accumulation contributes to tumor progression.
Journal ArticleDOI

Principles and current strategies for targeting autophagy for cancer treatment.

TL;DR: The current understanding of the core components of the autophagy machinery and the functional relevance of autophile within the tumor microenvironment is described and how this knowledge has informed preclinical investigations combining the autophile inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy, and immunotherapy is outlined.
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