IndraLab
Statements
Hydroxychloroquine inhibits autophagy. 695 / 699
|
53
642
reach
"Consistent with this hypothesis, a cytoprotective role of autophagy in established tumors exposed to stressors like anticancer treatments is suggested in studies where autophagy inhibitors like hydroxychloroquine or 3-methyladenine (3-MA) sensitize cancer cells to treatments like tamoxifen treatment, radiation, DNA alkylating agents cylophosphamide and cisplatin, and tyrosine kinase receptor inhibitor imatinib."
reach
"Chi et al. reported a 40% response rate and a 84% disease control rate by simultaneously adding the autophagy inducer rapamycin and the autophagy inhibitor hydroxychloroquine in 25 patients with various tumor types presenting with intrinsic resistance to numerous MC regimens [XREF_BIBR]."
reach
"100 Despite the promising effect of CQ, 100 a recent phase I/II clinical trial combining HCQ with TMZ and radiation therapy, in patients with newly diagnosed GBM showed that the maximum tolerated dose of HCQ was unable to consistently inhibit autophagy and that dose limiting toxicity prevented the possibility of moving to higher doses of HCQ."
reach
"Wortmannin, 3-methyladenine (3-MA), and LY294002 block autophagosome formation by targeting class III PI3K at the autophagy initiation stage, and chloroquine (CQ), hydroxychloroquine (HCQ), monensin, and bafilomycin A1 are able to inhibit autophagy by preventing the fusion of autophagosomes and lysosomes [136]."
reach
"Given that autophagy inhibitors including HCQ have shown efficacy against many different types of viruses (31) including SARS-CoV-2 in CPE assays (12), we assessed the protective effect of a group of autophagy inhibitors including ROC-325, clomipramine, hycanthone, verteporfin, CQ, HCQ, and mefloquine in 384-well plates."
| DOI
reach
"Hypoxia induced resistance of lung tumor to cytolytic T lymphocyte (CTL)-mediated lysis was demonstrated to be associated with autophagy induction, and inhibition of autophagy by HCQ dramatically reduced tumor growth in B16-F10 tumor bearing mice and restored the susceptibility of hypoxic tumor cell to CTL mediated lysis [XREF_BIBR]."
reach
"This has generated significant interest in autophagy inhibition as a therapeutic strategy in cancer; recently, anti-malarials, such as hydroxychloroquine (HCQ), which impair autophagy by disrupting lysosomal function, have been repurposed as autophagy inhibitors in multiple clinical trials for the treatment of advanced cancers."
reach
"HCQ was shown to successfully inhibit autophagy, as evidenced by the significant accumulation of autophagic vacuoles in peripheral blood mononuclear cells (mean autophagic vacuole counts : 2.19 at baseline, 2.45 after HCQ treatment, 3.84 after treatment with HCQ plus TMZ [difference between HCQ plus TMZ and baseline : p = 0.0007, difference between HCQ plus TMZ and HCQ only : p = 0.0034])."
reach
"Furthermore, unfortunately, single proteasome inhibitor treatment has been proven unsatisfactory for solid tumors in clinical trials.5, 6 A recent clinical trial suggested that the anticancer effect of Bor is enhanced when it is combined with an autophagy inhibitor.7 To date, autophagy inhibitors including hydroxychloroquine (HCQ) and chloroquine (CQ) have been clinically viable."
reach
"However, other Phase I/II clinical trials indicate that the problems of specificity and potency with hydroxychloroquine will need to be addressed with more selective and potent autophagy inhibitors for optimal anticancer treatment.Regarding the treatment of AML, the cytotoxic effect of autophagy inhibitors HCQ and/or baflomycin A1 (BafA1) is most evident in U937 cell lines Ara-C chemoresistant [204] and KG-1 compared to HL-60 cells when treated with ATO and ATRA [205]."
reach
"Our findings suggest that HCQ impaired the basal autophagic flux and inhibited autophagy, but BC001 did not affect HCQ-inhibited autophagy.To understand how HCQ or BC001 inhibits the growth of gastric cancer, we used RNA-Seq to identify DEGs in BGC823 cells treated with HCQ and/or BC001."
reach
"More recently, two second generation autophagy inhibitors, Lys05 a highly potent lysosometric agent and PIK-III a selective inhibitor of VPS34, demonstrated synergistic effects with TKIs to reduce primary CML LSCs quiescence, compared to the first generation autophagy inhibitor Hydroxychloroquine [XREF_BIBR]."
reach
"More studies focused on the molecular mechanisms underlying the functional effects of p53 mutants are needed to develop effective personalized therapeutic strategies based on the distinct types of TP53 mutation.In the context of autophagy, a previous study showed that autophagy inhibition by hydroxychloroquine and knockdown of ATG5 or ATG7 decreased tumor cell survival in AML harboring wild-type TP53, but not in mutated TP53 [119]."
reach
"Aspirin inhibits the proliferation, invasion, and metastasis of residual VX2 tumors through an anti-inflammatory effect.141 RFA and the antimalarials, chloroquine (CQ)/hydroxychloroquine (HCQ), inhibit the autophagy, proliferation, and stemness of tumor cells and promote their apoptosis.142, 143, 144 This effect can be enhanced by combining CQ and c-Met inhibitors.48 Metformin reduces the proliferation, migration, and invasion of HCC cells,145 and the expression of stem cell markers.46 All-trans retinoic acid (ATRA) eliminates tumor-initiating cells through the PI3K/AKT pathway."
reach
"The number and size of the autophagosomes (dark arrows) were progressively enhanced in control, bortezomib alone, HCQ alone, and combined treatment (Figure 5), indicative of the positive modulation of the autophagic pathway by bortezomib.Next, we asked whether the inhibition of proteasome by bortezomib and the blockade of autophagy by HCQ affected the proliferation (and viability) of PCs and ECs in MGUS and MM patients (Figure 6)."
reach
"Ongoing and planned studies will further address the possibility of better elucidating and fingerprinting autophagy marker levels in a dynamic fashion to accurately assess changes during the different steps of the autophagy process in any given biological setting.Overall, our data show that while combination treatment with bortezomib and HCQ significantly downregulates autophagy in myeloma PCs promoting PC death, it also positively modulates autophagy in ECs, supporting their survival."
reach
"Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged and oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs."
| PMC
reach
"Thus, autophagy inhibitors, such as HCQ, when used in association with bortezomib, may induce this response in resistant myeloma PCs, although an anti-angiogenic drug must be included to achieve a complete remission, as the simultaneous pro-angiogenic effect could, in fact, promote the proliferation of a small residual tumor PC clone to cause relapse.Accordingly, our study should be followed by further translational investigations of the role of therapeutic suppression in autophagy modulation."
reach
"Regrettably, due to the lack of tubule-specific agonists of the autophagy-lysosomal pathway, we could not prove that rescue of the autophagy-lysosomal pathway decreases the susceptibility to AKI in the mice with proteinuric LN and HCQ preadministration, which should be performed in the future.As mentioned above, we found that a long-term therapeutic dose of HCQ for LN may disrupt autophagy and promote senescence in PTECs to increase the susceptibility to AKI."
| PMC
eidos
"This has generated significant interest in autophagy inhibition as a therapeutic strategy in cancer ; recently , anti-malarials , such as hydroxychloroquine ( HCQ ) , which impair autophagy by disrupting lysosomal function , have been repurposed as autophagy inhibitors in multiple clinical trials for the treatment of advanced cancers ( Chude and Amaravadi , 2017 ) ."
reach
"Furthermore, because patients with Copa syndrome show an increase in autophagy with abnormal autophagosomes, hydroxychloroquine, which prevents autophagy by inhibiting lysosomal acidification and impairing fusion of the autophagosome with the lysosome, may also be useful for therapy for Copa syndrome."
reach
"Combining downstream MEK inhibition with hydroxychloroquine - an inhibitor of autophagy - displayed synergistic anti-proliferative effects against pancreatic ductal adenocarcinoma (PDA) cell lines and promoted striking regression of PDA xenografts from 2 patients with PDA which was superior to (standard of care) gemcitabine plus nab-paclitaxel chemotherapy."
reach
"Rapamycin can inhibit the proliferation, induce apoptosis and autophagy of RPMI 8226, the hydroxychloroquine can inhibit autophagy and proliferation of RPMI 8226, and induce apoptosis, the 3-MA can inhibit autophagy of RPMI 8226, but hardly has any effects on proliferation and apoptosis of RPMI 8226 cells."
eidos
"We also observed that the induction of apoptosis was greater with the combination of sorafenib and HCQ in only the S45F-mutated DT cell strains as compared to either treatments alone ( Fig. 5A ) , suggesting that autophagy blockade by HCQ enhances the antitumor activity of sorafenib in S45F-mutated DT cells ."
reach
"The drug Hydroxychloroquine is known for its ability to inhibit autophagy, by limiting the fusion of lysosomes and autophagosomes.99 Haas et al studied the efficacy and safety of combining Hydroxychloroquine and Everolimus in a cohort of 33 patients that had already failed previous therapy lines."
reach
"Despite this, we acknowledge that multiple immune cells play roles in orchestrating the immune response such that CQ can decrease the immunosuppressive infiltration of myeloid-derived suppressor cells and Treg cells [73] and HCQ inhibition of autophagy may synergize with dual anti-PD1 and anti-CTLA4 therapy [74]."
reach
"Preclinical studies have demonstrated that HCQ, the widely used antimalarial and antirheumatic drug, is a potent inhibitor of autophagy in cancer and increases tumor cell death alone or through enhancing tumor killing in combination with cytotoxic chemotherapy or targeted agents, mostly in patients with solid tumors, with the exception of cervical cancer."
reach
"Our previous work demonstrated that co-treatment with the autophagy inhibitor hydroxychloroquine (HCQ) could effectively block the last step of autophagy and enhance cell death induced by activation of p53 or treatment with alkylating chemotherapy in a model of Myc induced tumorigenesis."
reach
"Traditional antimalarials, chloroquine and hydroxychloroquine, known for their anti-inflammatory effects, are being repurposed to inhibit autophagy, potentially mitigating autophagic vacuole accumulation in lysosomal disorders like Danon disease, where dysfunctional autophagy leads to pathological cardiac hypertrophy [42]."
reach
"As mentioned above, HCQ is known to inhibit autophagy and is capable of sensitizing various tumors to the effects of chemotherapy, however, the nonselective distribution in vivo and the low capability to cross the BBB restrict its clinical use as well as the co-delivery of HCQ and ZD6474 in the treatment of glioma."
reach
"Fortuitously, the autophagy inhibitor hydroxychloroquine (a chloroquine derivative) has been used for many years in the management of patients with systemic lupus erythematosus, rheumatoid arthritis and malaria and therefore information about dosage, safety and side-effects has been available."
reach
"Autophagy inhibitors like chloroquine and hydroxychloroquine, as well as autophagy activators such as temsirolimus and rapamycin, have demonstrated efficacy in disrupting tumor growth, especially when combined with chemotherapy, according to both preclinical and clinical studies [164]."
reach
"The late-stage autophagy inhibitors, such as CQ, HCQ, bafilomycin A1, and lysosomal protease inhibitors, exert suppressive effects on downstream of autophagosome formation, including inhibition of autophagosome and lysosome fusion and/or blocking degradation of autophagic cargo inside autolysosomes [14]."
reach
"We recently determined that concurrent inhibition of ERK1/2 and autophagy synergistically suppressed the growth of KRAS-mutant PDAC, leading to our initiation of clinical trials to evaluate the combination of MEK or ERK inhibitor together with the autophagy inhibitor hydroxychloroquine."
reach
"Furthermore, selective triple knockdown of the autophagy genes ATG7, ATG5 and ATG3, and pre-treatment with the autophagy inhibitor hydroxychloroquine, efficiently overcame the resistance to Akt and mTOR inhibitors in this model, leading to the activation of the mitochondrial apoptotic pathway."
reach
"6
,
7
,
8
Therefore, it is an urgent need to inhibit the protective autophagy in cancer cells for cancer starvation therapy.To avoid the protective autophagy in cancer starvation therapy, researchers mainly utilize autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) to regulate the autophagy process."
reach
"However, despite the ability of HCQ to inhibit autophagy in patients, as evidenced by autophagosome accumulation on peripheral blood mononuclear and tumor cells [XREF_BIBR], its application in the clinical setting is limited by poor pharmacokinetics and frequent side effects [XREF_BIBR]."
reach
"Chloroquine and hydroxychloroquine directly inhibit autophagy by the alteration of lysosomal pH, inhibition of autophagic degradation, and accumulation of autophagosomes.109Table 2 lists some common anticancer natural compounds or synthetic drugs which can modulate the autophagy by different mechanisms."
reach
"Recent mechanistic combinatorial targeted therapy approaches, such as double inhibition of IGF1R and ERK signaling in organoid models, display increased sensitivity of pancreatic tumors to autophagy inhibitors such as hydroxychloroquine [66] and serve as a precedence to our concept."
reach
"Given the divergent conclusions of published studies regarding autophagy protein markers and autophagosome formation, the utility of autophagy inhibitors (lysosomotropic agents) such as chloroquine (CQ) or hydroxychloroquine (HCQ) in clinical trials for melanoma (either alone or as a combination therapy) supports conclusions in the literature that autophagy is a pro survival feature of melanomas, and so inhibiting the process pharmacologically is not only of clinical relevance, but a priority [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
reach
"Analysis showed that chloroquine/hydroxychloroquine inhibits autophagy in initial phases, causing accumulation of acidic vesicular organelles and break/discontinue autophagosome-lysosome fusions, but they do not alter the ability of lysosomes to digest target macromolecules as conventionally accepted."
reach
"CQ and HCQ inhibit autophagy and promote apoptosis of cancer cells, but they also work by affecting CXCR4-CXCL12 signaling, Toll-like receptor 9, and p53 in cancer cells, and tumor-associated fibroblasts and vessels as well immune responses in the tumor microenvironment retinopathy [76]."
reach
"Additionally, co-treated with QCT and autophagy inhibitors hydroxychloroquine (HCQ) which blocks autophagosome–lysosome fusion could promote the accumulation of protein LC3-II and P62, yet another early inhibitor of autophagy 3-MA could reverse QCT-induced up-regulation in the ratio of LC3-II/LC3-I."
reach
"The majority of chemotherapy agents and targeted therapeutics have been found to induce protective autophagy, resulting in reduced sensitivity to antitumor drugs, including traditional chemotherapy drugs (e.g., platinum compounds, 9 fluorouracil, 10 and etoposide 11) and molecular targeted agents As a consequence, autophagy inhibitors such as CQ (chloroquine) and HCQ (hydroxychloroquine) have been extensively investigated to potentiate the sensitivity to antitumor drugs."
reach
"Chloroquine (and its derivative hydroxychloroquine) inhibits autophagy, which is the proposed mechanism of its anti-ZIKV action since deficiency in an essential autophagy gene, Atg16l1, in mice limited ZIKV vertical transmission, placental and fetal damage, and improved placental and fetal outcomes overall."
eidos
"This has generated significant interest in autophagy inhibition as a therapeutic strategy in cancer ; recently , anti-malarials , such as hydroxychloroquine ( HCQ ) , which impair autophagy by disrupting lysosomal function , have been repurposed as autophagy inhibitors in multiple clinical trials for the treatment of advanced cancers ( Chude and Amaravadi , 2017 ) ."
eidos
"As mentioned above , HCQ is known to inhibit autophagy and is capable of sensitizing various tumors to the effects of chemotherapy , however , the nonselective distribution in vivo and the low capability to cross the BBB restrict its clinical use as well as the co-delivery of HCQ and ZD6474 in the treatment of glioma ( Gustafson et al ., 2006 ; Rangwala et al ., 2014 ; Rosenfeld et al ., 2014 ) ."
reach
"Additionally, HCQ is nonspecific autophagy inhibitor, and development of more specific and/or more potent autophagy inhibitors might be required to inhibit autophagy in BM-located cells in CML patients.We conclude that catalytic mTOR inhibitors may be effective for patients with BCR-ABL-independent resistance and that pharmacological autophagy inhibition will further enhance their efficacy."
reach
"Among the dynamic proteome induced by HCQ, NBR1, GABARAPL2, LGALS8, and MAPK8 are autophagy-related proteins, suggesting that HCQ may inhibit autophagy by tuning their expression.Cell pathway analysis showed that the upregulated proteins induced by HCQ are mainly enriched in the cellular metabolism process."
reach
"This is due to the enhanced binding of electrostatic interactions between CS and ALG in the acidic environment (Biswas et al., 2015), which slows drug release.It is clear that FeAC-DOX@PC-HCQ NPs protect the drug encapsulated in them well during blood transport, while HCQ and smaller NPs are better released when transported into the acidic tumour cell environment, where the released HCQ will act on its pharmacological target to inhibit autophagy and protect FeAC-DOX NPs from being removed by autophagy."
reach
"It was found that HCQ-induced autophagy inhibition can reprogram tumor-promoting M2-like TAMs to anti-tumor M1 phenotypes, thereby synergistically overcoming DOX resistance.Interestingly, nanotherapies that combine autophagy inducers with chemotherapeutic drugs can also yield enhanced chemotherapy results."
reach
"Autophagy inhibitors such as 3-MA (a class-III-PI3K inhibitor), bafilomycin A1, hydroxychloroquine and monensin (autophagosome-lysosome fusion inhibitors) have shown different efficacies in mitigating the effects of chemo- and radiotherapeutic anti-cancer treatments [XREF_BIBR], indicating the complexity with which this process is executed."
reach
"Although some clinical successes have been noted with chloroquine, a phase I/II clinical trial with the autophagy inhibitor hydroxychloroquine administered in combination with standard and adjuvant chemoradiotherapy failed to show a significant benefit in patients with newly diagnosed GBM."
reach
"In a relevant clinical trial in dogs with non Hodgkin 's lymphoma, the combined treatment of autophagy inhibitor hydroxychloroquine (12.5 mg/kg/d) with a lower dose of doxorubicin (25 mg/m 2) has resulted in clinical benefit with superior overall response rate (93.3%) and comparable median progression-free interval (5 months) compared to standard single agent doxorubicin (30 mg/m 2) treatment [XREF_BIBR]."
reach
"Since bafilomycin A1 could have non-autophagy-related activities, we performed confirmatory experiments with additional autophagy inhibitors including hydroxychloroquine sulfate (lysosomal acidification inhibitor), 3-methyladenine (3-MA, PI3K inhibitor), and MHY1485 (mTOR agonist)."
reach
"In clinical trials, HCQ has been used as an autophagy inhibitor for the treatment of advanced cancers [139,140], while preclinical studies have shown that CQ or HCQ can reduce tumor cell growth by inhibiting autophagy in cancer, bladder cancer, pancreatic cancer, lung cancer, and glioma [141,142,143,144]."
reach
"Pharmacological suppression of autophagy by chloroquine (CQ) and its derivant hydroxychloroquine (HCQ) results in reactive oxygen species (ROS) upregulation, DNA impairment, and mitochondria dysfunction, ultimately inhibiting cell growth in vitro as well as in xenografts (Yang et al., 2011, 2014)."
reach
"The combination of autophagy inhibitors with RA could be a promising therapeutic schedule to improve the efficacy of RA on GC treatment.It is speculated that HCQ may inhibit autophagy in a variety of tumors and have a synergistic effect with chemotherapeutic drugs, which is a potential research direction."
eidos
"Introduction Hydroxychloroquine ( Plaquenil ) is an aminoquinoline that is commonly used to treat malaria and a variety of rheumatic and dermatologic diseases , including systemic lupus erythematosus , rheumatoid arthritis , Sjogren syndrome , and porphyria cutanea tarda.1 ,2 In addition to its immunomodulatory effects , hydroxychloroquine has been noted to inhibit cellular autophagy ."
reach
"These compounds have been identified as cytoprotective autophagy inhibitors by targeting the classical PI3K complex, such as 3-methyladenine (3-MA), Wortmannin, and LY294002, which inhibit the early stage of autophagy, and autolysosomes, like chloroquine (CQ), hydroxychloroquine (HCQ), and bafilomycin A1, which primarily inhibit the late stage of autophagy (Bao et al., 2018; Collins et al., 2018; Wu et al., 2021)."
reach
"The combination of the autophagy inhibitor hydroxychloroquine with different drugs (gemcitabine, paclitaxel, carboplatin, etc.) or with mTOR inhibitors (rapamycin, everolimus, temsirolimus) is already used in several types of cancers, such as non small cell lung cancer (NSCLC), pancreatic cancer, renal cell carcinoma, myeloma and squamous cell cancer (head and neck cancer) (XREF_TABLE)."
reach
"Therefore, in some cancer cells, autophagy inhibition exerts anticancer effects; for example, chloroquine (CQ) and hydroxychloroquine (HCQ), which are inhibitors of autophagy that change lysosome acidification and inhibit autophagosome degradation by lysosomes, was combined with radiation and carmustine to treat glioblastoma in a phase III clinical trial [25]."
reach
"Recently, preclinical studies demonstrated that autophagy inhibition by hydroxychloroquine augments the efficacy of the proteasome inhibitor bortezomib in myeloma, indicating that the combination of autophagy and proteasome inhibition might be clinically useful for improving the outcomes of this neoplasia [XREF_BIBR, XREF_BIBR]."
reach
"Inhibition of autophagy by hydroxychloroquine, a well-tolerated autophagy inhibitor, reduced cell viability in both ETV6-RUNX1-positive cell lines and primary acute lymphoblastic leukemia samples, and selectively sensitized primary ETV6-RUNX1-positive leukemia samples to L asparaginase."
reach
"In March 2022, a search for the search term “autophagy and cancer” on the ClinicalTrials.gov website showed 91 studies, mainly focusing on inhibiting and evaluating autophagy to improve prognosis of cancer patients.As the only drugs used to inhibit autophagy in current clinical practice, CQ and hydroxychloroquine (HCQ) can prevent the degradation of cargo by deacidifying the lysosome and blocking the fusion of autophagosomes with lysosomes (132)."
reach
"Although autophagy inhibitors including chloroquine (CQ) and hydroxychloroquine have been used as monotherapy or in combination with chemo- or radiotherapy for cancer treatment including RCC (NCT01550367), the weak targeting ability and low biocompatibility of nonspecific autophagy inhibitors largely limit their clinical application [6]."
reach
"Hydroxychloroquine (HCQ) is an inhibitor of autophagy that has been studied in a randomized phase II trial in combination with gemcitabine and nab-paclitaxel; however, it showed no benefit compared to gemcitabine and nab-paclitaxel alone in terms of 12-month OS and median PFS (152)."
reach
"Based on the different types of inhibitory analyses, 10mM of the autophagy inhibitor 3-methyladenine (3-MA, Sigma-Aldrich Co., St. Louis, MO, USA), 100nM of the autophagy inhibitor bafilomycin A1 (ba A1, Sigma-Aldrich Co., St. Louis, MO, USA), 50muM of the autophagy inhibitor hydroxychloroquine (Selleck Chemicals, Houston, TX, USA), 5muM of the AKT inhibitor triciribine (Selleck Chemicals, Houston, TX, USA), 5muM of the PI3K agonist insulin like growth factors-1 (IGF-1, R&D Systems, Inc., Minneapolis, USA), 5muM of the PI3K inhibitor LY294002 (Selleck Chemicals, Houston, TX, USA), and 1muM of the mTOR inhibitor rapamycin (Rapa, Selleck Chemicals, Houston, TX, USA) were added to the culture medium together with HSYA for 4h."
reach
"To differentiate this, we treated the MCL cell line Mino with palbociclib and the downstream autophagy inhibitor hydroxychloroquine which inhibits the acidification of lysosomes, completely blocks autophagy in its final step and therefore leads to the accumulation of autophagosomes [XREF_BIBR]."
reach
"Given that autophagy inhibitors including HCQ have shown efficacy against many different types of viruses including SARS-CoV-2 in CPE assays, we assessed the protective effect of a group of autophagy inhibitors including ROC-325, clomipramine, hycanthone, verteporfin, CQ, HCQ, and mefloquine in 384-well plates (XREF_FIG)."
reach
"Herein, we describe our current understanding of the core components of the autophagy machinery, the functional relevance of autophagy within the tumor microenvironment and outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy and immunotherapy."
reach
"To examine if palmitoylation regulates GNA13 protein stability through these systems, we tested whether the downregulation of the GNA13 C14/18S mutant could be rescued by treatment with the proteasomal inhibitor MG132, the autophagy inhibitors HCQ and ULK-101, and several caspase inhibitors."
reach
"Indeed, numerous clinical trials utilizing HCQ in combination with cytotoxic and targeted therapies are under evaluation in various cancers; the first of these studies indicate that HCQ can be successfully employed to therapeutically inhibit autophagy in cancer patients with minimal dose limiting toxicities."
reach
"The released HCQ reduced the resistance of cancer cells to heat by repressing autophagy, making the cells more sensitive to mild hyperthermia, while the generation of Cyp-Y-NP increased the localization and accumulation of cypate within tumor cells, both contributing to the enhanced photothermal effect under NIR light irradiation."
reach
"28
Clinical trials combining chemotherapeutic agents with autophagy inhibitors such as chloroquine (CQ), hydroxychloroquine (HCQ) and 3‐methyladenine (3‐MA) provide survival benefits and increased life span in patients with breast cancer, myeloma, prostate cancer, and several other advanced tumors."
reach
"An ongoing trial being conducted by M.D. Anderson Cancer Center is testing the autophagy inhibitor hydroxychloroquine along with the MEK inhibitor binimetinib for the treatment of patients with KRAS mutant metastatic pancreatic cancer (Clinicaltrials.gov Identifier : NCT04132505 (accessed on 24 February 2021))."
reach
"In fact, although autophagy inhibitors such as hydroxychloroquine (HCQ) have failed to improve outcome in combination with platinum-based chemotherapy (Malhotra et al., 2019) in NSCLC patients, their potential role in inducing HLA or PD-L1 upregulation and the absence of impairment of T cell function by systemic inhibition of autophagy (Starobinets et al., 2016) are hypothesis-generating bases for further clinical investigation of non-selective (i.e., HCQ) or selective (i.e., ULK inhibitors) autophagy inhibitors in combination with PD-1/PD-L1 blockade."
reach
"Another pathway U0126 has been shown to interact with is the mTOR and autophagy pathway [XREF_BIBR, XREF_BIBR], given that HCQ is known to inhibit autophagy, subsequent experiments to dissect out the specific mechanism through which U0126 is blocking the protective effects of HCQ should be explored."
reach
"As shown in Fig. 5E, Cyp-HCQ-Yp plus laser induced significant expression and accumulation of the autophagy biomarker (LC3 II), validating the mechanism that HCQ disturbed the fusion of autophagosome with lysosome and inhibited the laser-triggered autophagy, for ultimate improvement of Cyp-mediated mPTT efficacy.Inspired by HSPs and autophagy inhibition strategy in overcoming the thermo-resistance of cancer cells, Shao et al. designed a multifunctional rattle-structured nanoparticle with the PDA core autophagy inhibitor chloroquine (CQ) loading and hollow mesoporous silica shell for GOx conjugation [48]."
reach
"Appropriate interpretation of the outcomes of these trials would require knowledge as to whether the drugs or radiation utilized promote the cytoprotective form of autophagy in the tumor cells as well as whether the chloroquine or hydroxychloroquine actually inhibited the autophagy."
reach
"Accordingly, in dnPI3K mice, TFEB target genes related to lysosome biogenesis were upregulated (Figure S13A), suggesting enhanced TFEB activity.To examine whether a cause-effect relationship exists between increased autophagy and cardiac health in aged dnPI3K mice, 19-month-old transgenic mice and their WT littermates received daily intraperitoneal injections of HCQ (60 mg/kg) to chronically inhibit autophagy in vivo (Figure S10C)."
reach
"Another lead-in safety study followed by a phase II trial of HCQ+D+T in patients with advanced BRAFV600-mutant melanoma also demonstrated that HCQ can prevent autophagy-driven resistance and, therefore, enhance the efficacy of BRAF-/MEK-inhibitor therapy in a “rechallenge” setting [238]."
reach
"We also observed that the induction of apoptosis was greater with the combination of sorafenib and HCQ in only the S45F-mutated DT cell strains as compared to either treatments alone (Fig. 5A), suggesting that autophagy blockade by HCQ enhances the antitumor activity of sorafenib in S45F-mutated DT cells."
reach
"In conclusion, this study revealed the dynamic proteome induced by HCQ and identified the potential target proteins of HCQ, which not only presents possible mechanisms underlying HCQ-induced autophagy inhibition but may also shed light on the link between HCQ and pancreatic cancer treatment."
reach
"Although a number of studies have demonstrated that autophagy may sensitize certain tumor cells to chemotherapeutic agents [XREF_BIBR - XREF_BIBR], the clinical applications of autophagy inhibitors such as CQ and hydroxychloroquine have been limited by their efficacy and side effects [XREF_BIBR, XREF_BIBR]."
reach
"These findings are currently under clinical investigation with several studies examining whether pharmacologic inhibition of autophagy with the anti-malaria and non specific autophagy inhibitor hydroxychloroquine augments the efficacy of standard anticancer regimens [XREF_BIBR - XREF_BIBR]."
reach
"CQ or HCQ, which are quinoline based drugs, are known as anti-malarial drugs and inhibit late autophagy by interfering with fusion between the autophagosome and lysosome by increasing lysosome pH. In recent years, quinoline based drugs have used as anti-inflammatory agents for rheumatoid arthritis, lupus erythematous, cancer, and sarcoidosis as well as some dermatologic conditions."
reach
"A meta-analysis concluded that autophagy inhibitors, such as CQ and HCQ, combined with other anticancer agents, could significantly increase overall response rate (ORR), 1-year overall survival (OS) rate, and 6-month progression-free survival (PFS) rate, improving survival of patients with cancer XREF_BIBR."
| PMC
reach
"Pre-clinical strategies targetingthe increase of pro tumorigenic autophagy response culminates in the use of various autophagy inhibitors like CQ (chloroquine) and HCQ (hydroxychloroquine) along with chemotherapeutics and radiotherapy to induce apoptosis48.For example, CQ enhanced temozolomide toxicity byreducing chemo-tolerance by blocking the pro survivalautophagic process, thereby helping glioma proliferation and therapy resistance49."
reach
"Additional autophagy relevant factors include inhibition of AXL kinase which decreases cytoprotective autophagic flux and induces immunogenic cell death in drug-resistant NSCLC cells [16] Moreover, chloroquine and hydroxychloroquine can inhibit cytoprotective autophagy by interfering with autophagic flux, thereby promoting the sensitization of cancer cells to chemotherapy [17]."
reach
"Chloroquine (CQ) and hydroxychloroquine (HCQ) are known to inhibit autophagy and have been investigated in preclinical studies and in more than 30 clinical trials; however, the ocular toxicities and minimal single-agent anticancer efficacy of CQ or HCQ have restricted their clinical application."
reach
"Autophagy modulation of the immune system has also been implicated in tumour growth with immune tolerance, macrophage recruitment and MHC-1 expression on tumour cells showing regulation by autophagic processes.In the studies presented here, we compare the sensitivity of hOSA and cOSA cell lines to antiproliferative and cytotoxic effects of the autophagy inhibitors hydroxychloroquine (HCQ) and Lys05."
reach
"The most recent reports have shown that the autophagy inhibitor hydroxychloroquine is tolerable and potentially effective in combination with the MTOR targeted agent temsirolimus [XREF_BIBR] and the proteasome inhibitor bortezomib [XREF_BIBR] in phase I trials (www.clinicaltrials.gov)."
reach
"We have previously shown that autophagy is rapidly induced following TKI treatment in CML cells and pharmacological autophagy inhibition, using the nonspecific autophagy inhibitor hydroxychloroquine (HCQ; inhibits autophagy at a late stage by preventing the fusion of autophagosomes and lysosomes), enhances the effect of TKI treatment in CML cells, including primary CD34 + stem or progenitor cells."
reach
"First, we identified that Pin1 degradation induced by the agents was likely due to the proteasome, based on the observation that Pin1 degradation was reversed by combination treatment of cell lines with the proteasome inhibitors carfilzomib (CFZ) or bortezomib (BTZ), while autophagy inhibitors hydroxychloroquine (HCQ) or bafilomycin A1 (Baf A1) were ineffective (Fig. 6)."
reach
"The latest reports have shown that the autophagy inhibitor hydroxychloroquine is tolerable and potentially effective in combination with the MTOR targeted agent temsirolimus XREF_BIBR and the proteasome inhibitor bortezomib XREF_BIBR in phase I trials and may be a valid complement to STAT3 targeted therapy."
reach
"In light of the sensitizing effect of autophagy inhibition on chemotherapy induced cell death, a number of clinical trials have been launched combining the first generation autophagy inhibitor hydroxychloroquine (HCQ) with individual chemotherapeutic agents in patients with solid tumors."