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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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Journal ArticleDOI

Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells.

TL;DR: In conclusion, inhibition of autophagy may be a therapeutic strategy to overcome acquired resistance of gefitinib in EGFR mutation NSCLC patients.
Journal ArticleDOI

Chloroquine exerts neuroprotection following traumatic brain injury via suppression of inflammation and neuronal autophagic death

TL;DR: In vivo evidence is provided that CQ may exert neuroprotective effects following TBI, in attenuating brain edema and improving neurological functioning, by reducing the damaging consequences of neuronal autophagy and cerebral inflammation.
Journal ArticleDOI

Combining AKT inhibition with chloroquine and gefitinib prevents compensatory autophagy and induces cell death in EGFR mutated NSCLC cells

TL;DR: It is shown that AKT inhibition, most importantly AKT2 inhibition, synergises with EGFR TKI inhibition to increase cell killing in EGFR M+ NSCLC cells, but the synergistic pro-apoptotic effects may be stunted due to a prosurvival autophagy response induced byAKT inhibition.
Journal ArticleDOI

Chloroquine-Modified Hydroxyethyl Starch as a Polymeric Drug for Cancer Therapy

TL;DR: Hydroxyethyl starch modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer cells has the potential as a drug delivery platform suitable for future development with chemotherapeutics to establish novel antimetastatic treatments.
Journal ArticleDOI

Inhibition of autophagy by chloroquine induces apoptosis in primary effusion lymphoma in vitro and in vivo through induction of endoplasmic reticulum stress

TL;DR: It is shown here for the first time that the inhibition of autophagy induces ER stress-mediated apoptosis in PEL cells, a novel strategy for cancer chemotherapy.
References
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Journal ArticleDOI

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Journal ArticleDOI

Acute Kidney Injury Network: Report of an Initiative to Improve Outcomes in Acute Kidney Injury

TL;DR: The Acute Kidney Injury Network (AKI Network) as discussed by the authors is a multidisciplinary collaborative network focused on AKI, which was established to improve care for patients with or at risk for AKI.
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

Autophagy: Renovation of Cells and Tissues

TL;DR: It is explored how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease.
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