Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: June 23, 2022

Cancer is one of the leading causes death worldwide. Several treatments are available for cancer treatment, but many treatment methods ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions This review describes known MDR mechanisms in cells and discusses ongoing laboratory approaches novel strategies that aim inhibit, circumvent, or reverse development various types. In this review, we discuss both intrinsic acquired drug resistance, addition highlighting hypoxia- autophagy-mediated mechanisms. factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced efflux, cell inhibition, other molecular cellular mechanisms, responsible anticancer agents. Drug can also depend on autophagic hypoxic status. The expression drug-resistant genes regulatory determine discussed. Methods circumvent MDR, immunoprevention, use microparticles nanomedicine might result better fighting

Language: Английский

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Cancer-associated fibroblasts-derived IL-8 mediates resistance to cisplatin in human gastric cancer

Cancer Letters, Journal Year: 2019, Volume and Issue: 454, P. 37 - 43

Published: April 9, 2019

Chemoresistance remains the major obstacle to achieve optimal prognosis in gastric cancer patients, and underlying molecular mechanisms of cancer-associated fibroblasts (CAFs) chemoresistance remain poorly understood. We identified high pretherapeutical serum IL-8 level patients was associated with poor response platinum-based therapy, it increased gradually during neoadjuvant chemotherapy decreased after radical surgery. Immunohistochemistry assays showed that highly expressed tissues chemoresistant located CAFs. Primary CAFs produced more than corresponding normal fibroblasts, human stomach fibroblast line Hs738 secreted co-cultured conditioned media from AGS or MGC-803 cells. IC50 cisplatin (CDDP) vitro. Simultaneously, treatment enhanced expression PI3K, phosphorylated-AKT (p-AKT), phosphorylated-IKb (p-IKb), phosphorylated-p65 (p-p65) ABCB1, ABCB1 p-p65 were overexpressed tumor patients. Collectively, derived promotes via NF-κB activation up-regulation. Our study provides a novel strategy improve chemotherapeutical efficacy cancer.

Language: Английский

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A Forward Vision for Chemodynamic Therapy: Issues and Opportunities

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(7)

Published: Jan. 17, 2023

Abstract Since the insight to fuse Fenton chemistry and nanomedicine into cancer therapy, great signs of progress have been made in field chemodynamic therapy (CDT). However, exact mechanism CDT is obscured by unique tumor chemical environment inevitable nanoparticle‐cell interactions, thus impeding further development. In this Scientific Perspective, significance clarified, complex deconstructed primitive biological research directions based on kinetics signaling pathways are discussed detail. Moreover, beneficial outlooks presented enlighten evolution next‐generation CDT. Hopefully, Perspective can inspire new ideas advances for provide a reference breaking down interdisciplinary barriers nanomedicine.

Language: Английский

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Magnetic nanoparticles for cancer theranostics: Advances and prospects

Journal of Controlled Release, Journal Year: 2021, Volume and Issue: 335, P. 437 - 448

Published: May 31, 2021

Language: Английский

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Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures

Cancer Cell International, Journal Year: 2022, Volume and Issue: 22(1)

Published: April 29, 2022

Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME) with diverse functions such as extracellular matrix (ECM) remodeling, modulation metabolism and angiogenesis, crosstalk both cancer cells infiltrating immune by production growth factors, cytokines, chemokines. Within TME milieu, CAFs exhibit morphological functional transitions relatively specific markers hold tremendous potential to facilitate tumorigenesis, development, resistance towards multiple therapeutic strategies including chemotherapy, radiotherapy, targeted therapy, anti-angiogenesis immunotherapy, endocrine therapy. Accordingly, themselves downstream effectors and/or signaling pathways targets for optimizing sensitivity anti-cancer therapies. This review aims provide a detailed landscape role that play in conferring different cancers underlying mechanisms. The translational perspectives individualized treatment malignant tumors also discussed.

Language: Английский

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Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS-sensing pathway

Cell, Journal Year: 2023, Volume and Issue: 186(11), P. 2361 - 2379.e25

Published: May 1, 2023

Language: Английский

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The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis

Biomimetics, Journal Year: 2023, Volume and Issue: 8(2), P. 146 - 146

Published: April 5, 2023

The extracellular matrix (ECM) is a ubiquitous member of the body and key to maintenance tissue organ integrity. Initially thought be bystander in many cellular processes, has been shown have diverse components that regulate activate processes ultimately influence cell phenotype. Importantly, ECM’s composition, architecture, stiffness/elasticity phenotypes. Under normal conditions during development, synthesized ECM constantly undergoes degradation remodeling via action proteases maintain homeostasis. In pathological including fibrosis cancer, synthesis, remodeling, dysregulated, causing its integrity altered. Both physical chemical cues from are sensed receptors integrins play roles driving proliferation differentiation progression various diseases such as cancers. Advances ‘omics’ technologies seen an increase studies focusing on bidirectional cell–matrix interactions, here, we highlight emerging knowledge role played by development conditions. This review summarizes current ECM-targeted therapies can modify tumors overcome drug resistance better cancer treatment.

Language: Английский

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Emerging role of NRF2 in ROS-mediated tumor chemoresistance

Biomedicine & Pharmacotherapy, Journal Year: 2020, Volume and Issue: 131, P. 110676 - 110676

Published: Aug. 25, 2020

Chemoresistance is a central cause for the tumor management failure. Cancer cells disrupt redox homeostasis through reactive oxygen species (ROS) regulatory mechanisms, leading to progression and chemoresistance. The transcription factor nuclear erythroid 2-related 2 (NRF2) master regulator of neutralizing cellular ROS restoring balance. Understanding role NRF2 in ROS-mediated chemoresistance can be helpful development chemotherapy strategies with better efficiency. In this review, we sum up roles classical agents including cisplatin, 5-fluorouracil, gemcitabine, oxaliplatin, paclitaxel, doxorubicin, how overcome by targeting NRF2. Finally, propose that might promising strategy resist ROS-driven acquire efficacy cancer treatment.

Language: Английский

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Reversal of Multidrug Resistance in Cancer by Multi-Functional Flavonoids

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: June 12, 2019

Multidrug resistance (MDR) resulting from different defensive mechanisms in cancer is one of the major obstacles clinical treatment. To circumvent MDR many reversal agents have been developed, but most them failed trials due to severely adverse effects. Recently, certain natural products reported overcome MDR, including flavonoids which are abundant plants, foods and herbs. Structure can be abbreviated as C6-C3-C6 (C for carbon), further categorized into flavonoids, iso-flavonoids, neo-flavonoids according their structural backbones. Flavonoids possess multiple bioactivities, a growing body research has indicated that both iso-flavonoids either kill or re-sensitize conventional chemotherapeutics resistant cells. Here, we summarize discuss underlying mechanisms, concluding these do not function specific regulators target proteins, rather multi-functional negatively regulate key factors contributing MDR.

Language: Английский

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Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature

Cancers, Journal Year: 2019, Volume and Issue: 11(9), P. 1284 - 1284

Published: Aug. 31, 2019

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized increased expression and activity mechanisms promoting survival, proliferation, metastatic spread. The present review summarizes current literature regarding use anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with focus on resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many characteristics desirable for drug: good proven toxicity profile, pharmacokinetics allowing reach therapeutic concentrations at disease site, ease administration low price. Several vitro studies suggest that MBZ inhibits wide range factors involved progression such tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, multi-drug resistance protein transporters. not only exhibits direct cytotoxic activity, but also synergizes ionizing radiations different chemotherapeutic agents stimulates antitumoral immune response. In vivo, single agent or combination chemotherapy led reduction complete arrest growth, marked decrease spread, improvement survival. Further investigations are warranted confirm clinical anti-neoplastic its safety other drugs setting.

Language: Английский

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