Autophagy as a molecular target for cancer treatment

European Journal of Pharmaceutical Sciences, Journal Year: 2019, Volume and Issue: 134, P. 116 - 137

Published: April 11, 2019

Language: Английский

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Distinctive properties of metastasis-initiating cells

Genes & Development, Journal Year: 2016, Volume and Issue: 30(8), P. 892 - 908

Published: April 15, 2016

Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only tiny fraction these is capable forming overt metastases. The tremendous rate attrition during the process metastasis implicates existence rare and unique population metastasis-initiating (MICs). MICs possess advantageous traits that may originate in primary tumor but continue evolve dissemination colonization, including cellular plasticity, metabolic reprogramming, ability enter exit dormancy, resistance apoptosis, immune evasion, co-option other stromal cells. Better understanding molecular hallmarks will facilitate development deployment novel therapeutic strategies.

Language: Английский

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Survivin and Tumorigenesis: Molecular Mechanisms and Therapeutic Strategies

Journal of Cancer, Journal Year: 2016, Volume and Issue: 7(3), P. 314 - 323

Published: Jan. 1, 2016

Survivin is the smallest member of inhibitor apoptosis protein family, which has key roles in regulating cell division and inhibiting by blocking caspase activation.Survivin highly expressed most human cancers, such as lung, pancreatic breast relative to normal tissues.Aberrant survivin expression associated with tumor proliferation, progression, angiogenesis, therapeutic resistance, poor prognosis.Studies on underlying molecular mechanisms indicate that involved regulation cytokinesis cycle well participates a variety signaling pathways p53, Wnt, hypoxia, transforming growth factor, Notch pathways.In this review, recent progress understanding basis discussed.Therapeutic strategies targeting preclinical studies are also briefly summarized.

Language: Английский

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Cancer therapy in the necroptosis era

Cell Death and Differentiation, Journal Year: 2016, Volume and Issue: 23(5), P. 748 - 756

Published: Feb. 26, 2016

Necroptosis is a caspase-independent form of regulated cell death executed by the receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage domain-like (MLKL). Recently, necroptosis-based cancer therapy has been proposed to be novel strategy for antitumor treatment. However, big controversy exists on whether this type feasible or just conceptual model. Proponents believe that because necroptosis apoptosis use distinct molecular pathways, triggering could an alternative way eradicate apoptosis-resistant cells. This hypothesis preliminarily validated recent studies. some skeptics doubt intrinsic acquired defects necroptotic machinery observed in many Moreover, two other concerns are not inducers selective killing cells without disturbing normal it will lead inflammatory diseases. In review, we summarize current studies surrounding research discuss advantages, potential issues, countermeasures therapy.

Language: Английский

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Molecular chess? Hallmarks of anti-cancer drug resistance

BMC Cancer, Journal Year: 2017, Volume and Issue: 17(1)

Published: Jan. 5, 2017

The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse inevitable for many cancer patients, despite improvements in drugs their use over the last 40 years. Resistance to anti-cancer can be acquired several mechanisms within neoplastic cells, defined as (1) alteration drug targets, (2) expression pumps, (3) detoxification mechanisms, (4) reduced susceptibility apoptosis, (5) increased ability repair DNA damage, (6) altered proliferation. It clear, however, that changes stroma tumour microenvironment, local immunity also contribute resistance. Cancer cells do these one time, there considerable heterogeneity between tumours, necessitating an individualised approach treatment. As tumours are heterogeneous, positive selection drug-resistant population could help drive resistance, although cannot simply viewed overgrowth resistant cell population. such predicted from pre-existing genomic proteomic profiles, increasingly sophisticated methods measure then tackle patients. oncologist now required least step ahead cancer, process likened ‘molecular chess’. Thus, increasing role predictive biomarkers clinically stratify it becoming clear personalised strategies obtain best results.

Language: Английский

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Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy

Oxidative Medicine and Cellular Longevity, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 16

Published: June 10, 2019

Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in forms of reduced glutathione (GSH) oxidized (GSSG). The processes synthesis, transport, utilization, metabolism are tightly controlled to maintain homeostasis redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells order meet enhanced vicious proliferation; meanwhile, also have develop an increased defense system cope with higher oxidant state. Growing numbers studies implicated that altering associated multiple programmed cell death cells. In this review, we firstly focus on from perspectives distribution, transportation, metabolism. Then, discuss function process. Afterwards, summarize recent advance understanding mechanism by which plays key role death, including apoptosis, necroptosis, ferroptosis, autophagy. Finally, highlight glutathione-targeting therapeutic approaches toward cancers. A comprehensive review depletion provide insight into redox-based research concerning therapeutics.

Language: Английский

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Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery

International Journal of Surgery, Journal Year: 2022, Volume and Issue: 107, P. 106936 - 106936

Published: Sept. 20, 2022

Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there a lack an ideal predictive model for drug sensitivity postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play important role tumor progression, which has potential to be prognostic indicator after surgery.Twelve PCD (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis, oxeiptosis) were analyzed construction. Bulk transcriptome, single-cell genomics, clinical information collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, KM-plotter cohorts validate model.The machine learning algorithm established index (CDI) 12-gene signature. Validated five independent datasets, high CDI had worse prognosis surgery. Two molecular subtypes distinct vital biological processes identified by unsupervised clustering model. A nomogram performance was constructed incorporating features. Furthermore, associated immune checkpoint genes key microenvironment components integrated analysis bulk transcriptome. are resistant standard adjuvant regimens (docetaxel, oxaliplatin, etc.); however, they might sensitive palbociclib (an FDA-approved luminal cancer).Generally, we novel comprehensively analyzing diverse patterns, can accurately predict user-friendly website created facilitate application this prediction (https://tnbc.shinyapps.io/CDI_Model/).

Language: Английский

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The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Oct. 7, 2020

During tumorigenesis, cancer cells are exposed to a wide variety of intrinsic and extrinsic stresses that challenge homeostasis growth. Cancer display activation distinct mechanisms for adaptation growth even in the presence stress. Autophagy is catabolic mechanism aides degradation damaged intracellular material metabolite recycling. This activity helps meet metabolic needs during nutrient deprivation, genotoxic stress, factor withdrawal hypoxia. However, autophagy plays paradoxical role depending on stage tumor development. Early suppressor via potentially oncogenic molecules. advanced stages, promotes survival by ameliorating stress microenvironment. These roles intricate due their interconnection with other cellular pathways. In this review, we present broad view participation phases Moreover, important processes such as cell death, reprogramming, metastasis, immune evasion treatment resistance all contribute development, reviewed. Finally, contribution hypoxic deficient microenvironment regulation these hallmarks development more aggressive tumors discussed.

Language: Английский

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A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy

Cells, Journal Year: 2019, Volume and Issue: 8(7), P. 674 - 674

Published: July 3, 2019

Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, infection-mediated stresses. dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, neurodegeneration. This review describes the mechanisms of autophagy its associations with other cell death mechanisms, apoptosis, necrosis, necroptosis, autosis. has both positive negative infection, cancer, neural development, metabolism, cardiovascular health, immunity, iron homeostasis. Genetic defects such as static childhood encephalopathy neurodegeneration adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon X-linked myopathy excessive autophagy, sporadic inclusion body myositis. Further studies on different microbial infections could help to design develop novel therapeutic strategies against pathogenic microbes. progress prospects research activators suppressors, which be used intervention numerous diseases drugs protect human animal health.

Language: Английский

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Programmed Cell Death Tunes Tumor Immunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

The demise of cells in various ways enables the body to clear unwanted cells. Studies over years revealed distinctive molecular mechanisms and functional consequences several key cell death pathways. Currently, most intensively investigated programmed (PCD) includes apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis, autophagy, which has been discovered play crucial roles modulating immunosuppressive tumor microenvironment (TME) determining clinical outcomes cancer therapeutic approaches. PCD can dual roles, either pro-tumor or anti-tumor, partly depending on intracellular contents released during process. also regulates enrichment effector regulatory immune cells, thus participating fine-tuning anti-tumor immunity TME. In this review, we focused primarily discussed messengers regulating their intricate crosstalk with response TME, explored immunological consequence its implications future therapy developments.

Language: Английский

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