Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer

Cancers, Journal Year: 2020, Volume and Issue: 12(8), P. 2252 - 2252

Published: Aug. 12, 2020

Breast cancer (BC) is the most prevalent in women. BC heterogeneous, with distinct phenotypical and morphological characteristics. These are based on their gene expression profiles, which divide into different subtypes, among triple-negative breast (TNBC) subtype aggressive one. The growing interest tumor metabolism emphasizes role of altered glucose driving progression, response to treatment, its therapy resistance. Alterations characterized by increased uptake glucose, hyperactivated glycolysis, decreased oxidative phosphorylation (OXPHOS) component, accumulation lactate. deviations attributed upregulation key glycolytic enzymes transporters metabolic pathway. Key such as hexokinase, lactate dehydrogenase, enolase upregulated, thereby conferring resistance towards drugs cisplatin, paclitaxel, tamoxifen, doxorubicin. Besides, drug efflux detoxification two energy-dependent mechanisms contributing emergence chemotherapy can occur at an early or later stage thus limiting success outcome therapy. Therefore, understanding aberrant tumors link essential. Using combinatory treatment inhibitors, for example, 2-deoxy-D-glucose (2-DG) metformin, showed promising results countering Newer designs conjugated sugars peptides that utilize enhanced cell offer selective efficient delivery cells less toxicity healthy cells. Last but not least, naturally occurring compounds plants defined phytochemicals manifest a approach eradication via suppression essential other compartments associated glycolysis. Their benefits human health open new opportunities therapeutic intervention, either alone combination chemotherapeutic drugs. Importantly, efficacious instruments anticancer suppress events leading chemoresistance Here, we review current knowledge classical various ways target will serve strategy chemosensitizing overcoming BC.

Language: Английский

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The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 3, 2021

Although chemotherapy can improve the overall survival and prognosis of cancer patients, chemoresistance remains an obstacle due to diversity, heterogeneity, adaptability environmental alters in clinic. To determine more possibilities for therapy, recent studies have begun explore changes metabolism, especially glycolysis. The Warburg effect is a hallmark that refers preference cells metabolize glucose anaerobically rather than aerobically, even under normoxia, which contributes chemoresistance. However, association between glycolysis molecular mechanisms glycolysis-induced unclear. This review describes mechanism from aspects process, signaling pathways, tumor microenvironment, their interactions. understanding how induces may provide new targets concepts therapy.

Language: Английский

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Glucose Transporters as a Target for Anticancer Therapy

Cancers, Journal Year: 2021, Volume and Issue: 13(16), P. 4184 - 4184

Published: Aug. 20, 2021

Tumor growth causes cancer cells to become hypoxic. A hypoxic condition is a hallmark of cancer. Metabolism differs from metabolism normal cells. Cancer prefer the process glycolysis as source ATP. Process generates only two molecules ATP per one molecule glucose, whereas complete oxidative breakdown glucose yields 36 Therefore, need more in comparison with Increased uptake by these due overexpression transporters, especially GLUT1 and GLUT3, that are hypoxia responsive, well other transport proteins. expression carrier proteins may be used anticancer therapy. This phenomenon diagnostic techniques such FDG-PET. It also suggested, there observations, therapeutic inhibition transporters method treatment patients. On hand, described cases, which upregulation as, for example, NIS, radioiodine therapy, can help patients The aim this review presentation possibilities, how

Language: Английский

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Cancer metabolism and carcinogenesis

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 29, 2024

Abstract Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing adapt different microenvironments therapeutic interventions. This refers heterogeneity, in which cell populations use pathways sustain survival proliferation impact response conventional therapies. Thus, targeting heterogeneity represents innovative avenue with potential overcome treatment resistance improve outcomes. review discusses patterns developmental stages, summarizes molecular mechanisms involved intricate interactions within metabolism, highlights clinical vulnerabilities as a promising regimen. We aim unravel complex characteristics develop personalized approaches address distinct traits, ultimately enhancing patient

Language: Английский

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The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(2)

Published: Feb. 26, 2021

Abstract Mitochondria are essential cellular organelles that involved in regulating energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic metabolic disease closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which major molecules respond to hypoxia, play important roles development by participating multiple processes, such as proliferation, angiogenesis. The Warburg phenomenon reflects pseudo-hypoxic state activates HIF-1α. In addition, product of the effect, lactate, also induces However, proposed aerobic glycolysis occurs due defect mitochondria. Moreover, both HIFs dysfunction can lead complex reprogramming energy including reduced oxidative increased glucose uptake, enhanced anaerobic glycolysis. Thus, there may be connection between this review, we systematically discuss crosstalk dysfunctions development. Above all, stability activity influenced related tricarboxylic acid cycle, electron transport chain components, respiration, mitochondrial-related proteins. Furthermore, activation affecting functions, capacity, biogenesis, apoptosis, fission, autophagy. general, regulation tumorigenesis part an extensive cooperative network.

Language: Английский

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Reactive Glycolysis Metabolite‐Activatable Nanotheranostics for NIR‐II Fluorescence Imaging‐Guided Phototherapy of Cancer

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(23)

Published: March 7, 2022

Abstract Second near‐infrared (NIR‐II) fluorescence imaging with deep tissue‐penetration ability holds remarkable potential for cancer diagnosis. However, clinical translation of NIR‐II imaging‐based treatment is severely restricted by the low signal‐to‐background ratio due to insufficient tumor specificity fluorophores. In this study, it hypothesized that methylglyoxal (MGO), an intermediate metabolite glycolysis could be used as a potent biomarker triggering imaging‐guided theranostic. For proof‐of‐concept, first MGO‐activatable probe developed, and then MGO‐responsive “dual lock‐and‐key” nanotheranostics integrating fluorophore photodynamic prodrug (i.e., hexyl 5‐aminolevulinic acid hydrochloride (HAL)) into one nanoparticle engineered. The nanotheranostic can specifically activated tumorous MGO combinatory therapy. Upon 808 nm laser irradiation, generate tunable photothermal effect trigger HAL release. Subsequently, converted protoporphyrin IX inside cells 655 irradiation‐induced It demonstrated highly in efficiently suppressed 4T1 breast growth mouse model. might imply novel insight reactive metabolite‐activatable precise therapy tumor.

Language: Английский

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[Retracted] Detection of Breast Cancer Using Histopathological Image Classification Dataset with Deep Learning Techniques

BioMed Research International, Journal Year: 2022, Volume and Issue: 2022(1)

Published: Jan. 1, 2022

Cancer is one of the top causes mortality, and it arises when cells in body grow abnormally, like case breast cancer. For people all around world, has now become a huge issue threat to their safety wellbeing. Breast cancer major death among females over globe, particularly prevalent United States. It possible diagnose using variety imaging modalities including mammography, computerized tomography (CT), magnetic resonance (MRI), ultrasound, biopsies, others. To analyze picture, histopathology study (biopsy) often performed, which assists diagnosis The goal this develop improved strategies for various CAD phases that will play critical role minimizing variability gap between observers. created an automatic segmentation approach then followed by self‐driven post‐processing activities successfully identify Fourier Transform based Segmentation system improve its performance. When compared existing techniques, proposed technique several advantages: spatial information incorporated, there no need set any initial parameters beforehand, independent magnification, automatically determines inputs morphological operations enhance segmented images so pathologists can image with greater clarity, fast. Extensive tests were conducted determine most effective feature extraction techniques investigate how textural, morphological, graph characteristics impact accuracy categorization classification. In addition, classification strategy detection been developed on weighted selection uses upgraded version Genetic Algorithm conjunction Convolutional Neural Network Classifier. practical application suggested algorithms framework may reduce number incorrect diagnoses increase So, serve as second opinion tool aid early diseases.

Language: Английский

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HIF: a master regulator of nutrient availability and metabolic cross‐talk in the tumor microenvironment

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(6)

Published: Feb. 20, 2023

Language: Английский

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Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4646 - 4687

Published: May 13, 2024

This review systematizes information about the metabolic features of breast cancer directly related to oxidative stress. It has been shown those redox changes occur at all levels and affect many regulatory systems in human body. The biochemical processes occurring are described, ranging from nonspecific, first glance, strictly hormone-induced reactions, genetic epigenetic regulation, which allows for a broader deeper understanding principles oncogenesis, as well maintaining viability cells mammary gland. Specific pathways activation stress have studied response overproduction hormones estrogens, specific ways reduce its negative impact described. diversity participants that trigger reactions different sides is considered more fully: glycolytic activity cancer, nature consumption amino acids metals. role metals discussed detail. They can act both co-factors direct stress, since they either mechanism lipid peroxidation or capable activating signaling tumorigenesis. Special attention paid regulation tumors. A complex cascade mechanisms explained, made it possible reconsider existing opinion triggers launching oncological process, survival their ability localize.

Language: Английский

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Reprogramming of glucose metabolism: The hallmark of malignant transformation and target for advanced diagnostics and treatments

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117257 - 117257

Published: Aug. 12, 2024

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly reprogramming glucose metabolism, also known as "Warburg effect". The is considered a novel hallmark human cancers. A growing number studies have shown that can regulate many biological processes cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize major functions, clinical significance, potential targets signaling pathways metabolic in Moreover, applications natural products small molecule inhibitors targeting are analyzed, some agents trial statuses summarized, well pros cons for therapy analyzed. Overall, plays an important role prediction, prevention, diagnosis treatment Glucose reprogramming-related great to serve biomarkers improving individual outcomes prognosis patients. innovations related will be hotspot research future. We suggest more high-quality trials with abundant formulations toxicology experiments would beneficial development application drugs metabolism.This review provide researchers broader perspective comprehensive understanding about significance

Language: Английский

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