Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Cancers, Journal Year: 2021, Volume and Issue: 13(19), P. 4985 - 4985

Published: Oct. 5, 2021

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype mesenchymal to invade surrounding tissues. EMT physiological event during embryogenesis (type I) but also happens fibrosis II) and cancer metastasis III). It multifaceted phenomenon governed by activation genes associated with cell migration, extracellular matrix degradation, DNA repair, angiogenesis. The employ acquire ability migrate, resist therapeutic agents escape immunity. One key biomarkers vimentin, type III intermediate filament that normally expressed in upregulated metastasis. This review highlights pivotal role vimentin explains its as downstream well an upstream regulator this highly complex process. areas require further research exploring EMT. As cytoskeletal protein, filaments support mechanical integrity migratory machinery, generation directional force, focal adhesion modulation attachment. viscoelastic scaffold, it gives stress-bearing flexible organelles. However, modulates for inducers such Snail, Slug, Twist ZEB1/2, epigenetic factors. In addition, suppresses cellular differentiation upregulates their pluripotent potential inducing self-renewability, thus increasing stemness stem cells, facilitating tumour spread making them more resistant treatments. Several missense frameshift mutations reported human cancers may contribute towards metastatic spread. Therefore, we propose should be target using technologies will curb growth reduced mortality morbidity.

Language: Английский

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Molecular targeted therapy for anticancer treatment

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(10), P. 1670 - 1694

Published: Oct. 12, 2022

Abstract Since the initial clinical approval in late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served a fundamental backbone precision medicine cancer treatment. These approaches are now used clinically first-line various human cancers. Compared to conventional chemotherapy, have efficient with fewer side effects. However, emergence drug resistance is major drawback therapy, several strategies been attempted improve efficacy by overcoming such resistance. Herein, we summarize current knowledge regarding agents, including classification, brief biology target kinases, mechanisms action, examples perspectives future development.

Language: Английский

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The Role of EREG/EGFR Pathway in Tumor Progression

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 12828 - 12828

Published: Nov. 27, 2021

Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung cancer and colorectal (CRC). Epiregulin (EREG) is one EGFR low expressed in most normal tissues. Elevated EREG cancers mainly activates signaling pathways promotes progression. Notably, a higher expression level CRC with wild-type Kirsten rat sarcoma (KRAS) related better efficacy therapeutic treatment. By contrast, resistance anti-EGFR therapy was driven expression, aberrant genetic mutation signal pathway alterations. Additionally, overexpression non-small cell (NSCLC) anticipated be target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that derived from macrophages NSCLC EGFR-TKI The emerging events EREG-mediated promotion signals are generated autocrine paracrine loops arise epithelial cells, fibroblasts, microenvironment (TME). TME crucial element development types drug resistance. regulation EREG/EGFR depends on distinct oncogenic driver mutations contexts allows specific pharmacological targeting alone or combinational treatment tailored therapy. Novel strategies EREG/EGFR, tumor-associated macrophages, alternative oncoproteins under undergoing clinical trials. In this review, we summarize outcomes interaction ligand TME. may potential combined other targets combat cancers.

Language: Английский

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Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed circumvent tumor plasticity, including epigenetic modifications, regulation transcription factors, activation suppression key signaling pathways, as well modification environment. Epithelial-to-mesenchymal transition, stem formation also serve roads towards Corresponding treatment strategies recently developed that either target plasticity-related employ combination treatments. In this review, we delineate plasticity its manipulation evasion from therapy. We discuss non-genetic drug-induced various types tumors provide insights into contribution acquired drug resistance. New therapeutic such inhibition reversal are presented. multitude clinical trials ongoing worldwide with intention improving outcomes. These advances direction for developing novel therapy regimens

Language: Английский

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Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Cancers, Journal Year: 2022, Volume and Issue: 14(4), P. 976 - 976

Published: Feb. 15, 2022

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal cells, i.e., self-renewal differentiation potential, suggesting they can drive progression. Consequently, targeting to prevent tumor growth or regrowth might offer chance lead the fight against cancer. create their niche, specific area within tissue unique microenvironment sustains vital functions. Interactions between niches play critical role regulating CSCs' tumorigenesis. Differences observed frequency CSCs, due phenotypic plasticity many remain challenge therapeutics, since modulate transcriptional activities into more stem-like state protect themselves from destruction. This represents an essential step future therapeutic approaches. Regarding self-renewal, are modulated by same molecular pathways found such as Wnt/β-catenin signaling, Notch Hedgehog signaling. Another key characteristic resistance standard chemotherapy radiotherapy treatments, capacity rest quiescent state. review will analyze primary mechanisms involved CSC tumorigenesis, particular attention roles progression benign malignant diseases; examine perspectives on identification new markers better control well dissecting process.

Language: Английский

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Drug-Tolerant Persister Cells in Cancer Therapy Resistance

Cancer Research, Journal Year: 2022, Volume and Issue: 82(14), P. 2503 - 2514

Published: May 18, 2022

One of the current stumbling blocks in our fight against cancer is development acquired resistance to therapy, which attributable approximately 90% cancer-related deaths. Undercutting this process during treatment could significantly improve management. In many cases, drug mediated by a drug-tolerant persister (DTP) cell subpopulation present tumors, often referred as cells. This review provides summary currently known subpopulations and approaches target them. A specific DTP with elevated levels aldehyde dehydrogenase (ALDH) activity has stem cell-like characteristics high level plasticity, enabling them switch rapidly between low ALDH activity. Further studies are required fully elucidate functions ALDH-high cells, how they withstand concentrations that kill other adapt under cellular stress eventually lead more aggressive, recurrent, drug-resistant cancer. Furthermore, addresses processes used enable progression, isoforms important these processes, interactions DTPs tumor microenvironment, therapeutically modulate order effectively manage

Language: Английский

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Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Jan. 22, 2024

Abstract This comprehensive review delves into cancer’s complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression therapeutic strategies. covers cancer cell migration, invasion, colonization distant organs, emphasizing significance adhesion intricate metastasis process. Inhibition approaches targeting molecules, such as integrins cadherins, are discussed. Overall, this contributes significantly to advancing research developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising targets alleviate cells. The effectiveness integrin-blocking antibodies, small molecule inhibitors Focal kinase (FAK) Transforming Growth Factor β (TGF-β) pathway, combination therapies underscores their potential disrupt focal adhesions control epithelial-mesenchymal transition processes. identification FAK, Src, β-catenin SMAD4 offers valuable starting points further development therapies. complex interrelationships between metastatic signaling networks will be relevant new treatment approaches.

Language: Английский

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Programmable intratumoral drug delivery to breast cancer using wireless bioelectronic device with electrochemical actuation

Expert Opinion on Drug Delivery, Journal Year: 2024, Volume and Issue: 21(3), P. 495 - 511

Published: Feb. 24, 2024

Breast cancer is a global health concern that demands attention. In our contribution to addressing this disease, study focuses on investigating wireless micro-device for intratumoral drug delivery, utilizing electrochemical actuation. Microdevices have emerged as promising approach in field due their ability enable controlled injections various applications.

Language: Английский

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Digestive cancers: mechanisms, therapeutics and management

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 14, 2025

Abstract Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% annual cases cancer deaths. The etiologies, molecular features, therapeutic management these entities highly heterogeneous complex. Over last decade, genomic functional studies have provided unprecedented insights into biology cancers, identifying genetic drivers tumor progression key interaction points cells with immune system. This knowledge is continuously translated novel treatment concepts targets, which dynamically reshaping landscape tumors. In this review, we provide a concise overview etiology pathology six most common cancers system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, colorectal cancers. We comprehensively describe current stage-dependent pharmacological malignancies, chemo-, targeted, immunotherapy. For each entity, an recent advancements research progress. Finally, how heterogeneity evasion deepen our understanding therapy resistance outlook on innovative strategies that will shape future CAR-T cell therapy, antibody-drug conjugates targeted therapies.

Language: Английский

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Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness

Cancers, Journal Year: 2020, Volume and Issue: 12(12), P. 3716 - 3716

Published: Dec. 11, 2020

Tumor heterogeneity is considered the major cause of treatment failure in current cancer therapies. This feature solid tumors not only result clonal outgrowth cells with genetic mutations, but also epigenetic alterations induced by physical and chemical signals from tumor microenvironment (TME). Besides fibroblasts, endothelial immune cells, mesenchymal stroma/stem-like (MSCs) tumor-associated macrophages (TAMs) intimately crosstalk can exhibit both anti- pro-tumorigenic effects. MSCs alter cellular phenotypes to increase cell plasticity, eventually resulting generation stem (CSCs). The shift between different phenotypic states (phenotype switching) CSCs controlled via programs, such as epithelial-mesenchymal transdifferentiation or retrodifferentiation, triggered TME, like hypoxia, spatial stromal cell-derived chemokines. Finally, we highlight role spontaneous fusion various types cells. i.e., shaping CSC plasticity. A better understanding plasticity phenotype shifting a prerequisite for exploiting this phenomenon reduce heterogeneity, thereby improving chance therapy success.

Language: Английский

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