Chloroquine against malaria, cancers and viral diseases

Zhou, Wenmin; Wang, Hui; Yang, Yuqi; Chen, Zhe‐Sheng; Zou, Chang; Zhang, Jianye

doi:10.1016/j.drudis.2020.09.010

Cited by 82 publications

(61 citation statements)

References 107 publications

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“…Nowadays, chloroquine and hydroxychloroquine are used to treat autoimmune and connective tissue diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, palindromic rheumatism, eosinophilic fasciitis, dermatomyositis, cellulitis, mixed and undifferentiated connective tissue disease (11,13,14). They have also demonstrated anticancer properties against different types of cancer (e.g., colon, lung and breast cancer, central nervous system tumors, hematological malignancies), and against cancer cell lines in vitro (11,15). CQ has also demonstrated antiviral activity, and has been used in clinical trials in infections caused by hepatitis C virus, dengue virus-2, human immunodeficiency virus, and Chikungunya virus (15).…”

Section: Clinical Applications Of Antimalarial Drugsmentioning

confidence: 99%

“…They have also demonstrated anticancer properties against different types of cancer (e.g., colon, lung and breast cancer, central nervous system tumors, hematological malignancies), and against cancer cell lines in vitro (11,15). CQ has also demonstrated antiviral activity, and has been used in clinical trials in infections caused by hepatitis C virus, dengue virus-2, human immunodeficiency virus, and Chikungunya virus (15). Recently, CQ and CHQ were proposed as treatments for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and were prescribed for almost 12% of COVID-19 patients in Europe (16).…”

Section: Clinical Applications Of Antimalarial Drugsmentioning

confidence: 99%

See 1 more Smart Citation

The Ototoxicity of Antimalarial Drugs—A State of the Art Review

Józefowicz-Korczyńska

Pajor

Grzelczyk

2021

Front. Neurol.

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This review summarizes current knowledge about the occurrence of hearing and balance disorders after antimalarial drugs treatment. It also examines the clinical applications of antimalarials, their mechanisms behind this ototoxicity and how it can be monitored. It includes studies with larger numbers of patients and those in which auditory function was assessed using audiological tests. Some antimalarials have been repurposed for other conditions like autoimmune disorders, rheumatic diseases, some viral diseases and cancers. While old antimalarial drugs, such as quinoline derivatives, are known to demonstrate ototoxicity, a number of new synthetic antimalarial agents particularly artemisinin derivatives, demonstrate unknown ototoxicity. Adverse audiovestibular effects vary depending on the medication itself, its dose and route of administration, as well as the drug combination, treated disease and individual predispositions of the patient. Dizziness was commonly reported, while vestibular symptoms, hearing loss and tinnitus were observed much less frequently, and most of these symptoms were reversible. As early identification of ototoxic hearing loss is critical to introducing possible alternative treatments with less ototoxic medications, therefore monitoring systems of those drugs ototoxic side effects are much needed.

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Section: Clinical Applications Of Antimalarial Drugsmentioning

confidence: 99%

Section: Clinical Applications Of Antimalarial Drugsmentioning

confidence: 99%

The Ototoxicity of Antimalarial Drugs—A State of the Art Review

Józefowicz-Korczyńska

Pajor

Grzelczyk

2021

Front. Neurol.

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show abstract

“…As an adjuvant, CQ was shown to enhance clinical responses to anti-GBM therapy in double-blinded Phase III studies 68 . CQ was shown to be able to cross the blood-brain barrier in vivo 69–71 , while preclinical studies have demonstrated that concentrations of 50 mg/kg are suitable for administration regimens against orthotopic glioblastoma xenografts 72–74 . The multiple effects of CQ on the phenotypic signatures and chemokine profiles of GBM in vivo , alongside a limited ability to control tumor burden alone, however, point to a nuanced role in combination regimens which can nonetheless uniquely enhance CAR-based adoptive transfer immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Tumor-responsive, multifunctional CAR-NK cells cooperate with impaired autophagy to infiltrate and target glioblastoma

Wang

Torregrosa-Allen

Elzey

et al. 2020

Preprint

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Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking have rendered glioblastoma (GBM) highly resistant to therapy. As a result, GBM immunotherapies have failed to demonstrate sustained clinical improvements in patient overall survival (OS). To overcome these obstacles, here we describe a novel, sophisticated combinatorial platform for GBM: the first multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses key drivers of GBM resistance to therapy: antigen escape, poor immune cell homing, and immunometabolic reprogramming of immune responses. We engineered dual-specific CAR-NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally-released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site specific activity in the tissue and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells, but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising new NK cell-based combinatorial strategy that can target multiple clinically-recognized mechanisms of GBM progression simultaneously.

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“…As a new emerging hCoV, it is largely unknown how SARS-CoV-2 is targeted by or manipulates autophagy. Accumulating evidence suggests that SARS-CoV-2 infection may perturb the autophagic process ( localization [70,71]. It is doubtful that their putative effects on autophagy inhibition are necessarily causal for their anti-SARS-CoV-2 activity in specific cells.…”

Section: Sars-cov-2 Infection and Autophagymentioning

confidence: 99%

“…Unfortunately, their inhibitory efficiency did not extend to SARS-CoV-2 infected TMPRSS2-expressing human lung cells or animal models and COVID-19 patients [ 66–69 ]. It should be noted that lysosomotropic agents CQ and HCQ have many physiological functions, including blocking autophagosome-lysosome fusion, alkalizing endosomal/lysosomal acidification, and disrupting lipid clustering and ACE2 localization [ 70 , 71 ]. It is doubtful that their putative effects on autophagy inhibition are necessarily causal for their anti-SARS-CoV-2 activity in specific cells.…”

Section: Targeting Autophagy As a Promising Strategy For Covid-19mentioning

confidence: 99%

The interplay between emerging human coronavirus infections and autophagy

Zhao

Mao

et al. 2021

Emerging Microbes & Infections

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Following outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2002 and 2012, respectively, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic emerging human coronavirus (hCoV). SARS-CoV-2 is currently causing the global coronavirus disease 2019 (COVID-19) pandemic. CoV infections in target cells may stimulate the formation of numerous double-membrane autophagosomes and induce autophagy. Several studies provided evidence that hCoV infections are closely related to various cellular aspects associated with autophagy. Autophagy may even promote hCoV infection and replication. However, so far it is unclear how hCoV infections induce autophagy and whether the autophagic machinery is necessary for viral propagation. Here, we summarize the most recent advances concerning the mutual interplay between the autophagic machinery and the three emerging hCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 and the model system mouse hepatitis virus. We also discuss the applicability of approved and well-tolerated drugs targeting autophagy as a potential treatment against COVID-19.

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Chloroquine against malaria, cancers and viral diseases

Abstract: Graphical abstract The pleiotropic effects of chloroquine that including anti-malaria, anti-cancer and anti-viral diseases, which is linked with inhibition of autophagy, tumor vascular normalization, lysosomotropic and immunomodulatory property.

Cited by 82 publications

References 107 publications

The Ototoxicity of Antimalarial Drugs—A State of the Art Review

The Ototoxicity of Antimalarial Drugs—A State of the Art Review

Tumor-responsive, multifunctional CAR-NK cells cooperate with impaired autophagy to infiltrate and target glioblastoma

The interplay between emerging human coronavirus infections and autophagy

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