Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 10, 2024

Abstract Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and immunosuppressive nature microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components TME. M2-like TAMs are in facilitating metastasis as well augmenting tumors. This review encapsulates mechanisms that use to promote resistance. We also describe emerging therapeutic strategies currently targeting combination with other antitumor drugs, some still undergoing clinical trial evaluation. Furthermore, we summarize analyze various existing approaches for developing novel drugs target overcome resistance, highlighting how can effectively stop growth, metastasis,

Language: Английский

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Cancer cell heterogeneity and plasticity: A paradigm shift in glioblastoma

Neuro-Oncology, Journal Year: 2021, Volume and Issue: 24(5), P. 669 - 682

Published: Nov. 23, 2021

Phenotypic plasticity has emerged as a major contributor to intra-tumoral heterogeneity and treatment resistance in cancer. Increasing evidence shows that glioblastoma (GBM) cells display prominent intrinsic reversibly adapt dynamic microenvironmental conditions. Limited genetic evolution at recurrence further suggests mechanisms also largely operate the phenotypic level. Here we review recent literature underpinning role of GBM creating gradients heterogeneous including those carry cancer stem cell (CSC) properties. A historical perspective from hierarchical nonhierarchical concept CSCs towards appreciation is provided. Cellular states interact dynamically with each other surrounding brain shape flexible tumor ecosystem, which enables swift adaptation external pressure treatment. We present key components regulating equilibrium states, genetic, epigenetic, factors. discuss context resistance, where variable balance between preexisting resistant adaptive persisters leads reversible upon Innovative efforts targeting regulators state transitions treatment-resistant are needed restrict capacities GBM.

Language: Английский

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Integrated analysis of single-cell and bulk RNA sequencing data reveals a pan-cancer stemness signature predicting immunotherapy response

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: April 29, 2022

Although immune checkpoint inhibitor (ICI) is regarded as a breakthrough in cancer therapy, only limited fraction of patients benefit from it. Cancer stemness can be the potential culprit ICI resistance, but direct clinical evidence lacking.

Language: Английский

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Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 10, 2023

Abstract Mapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of biology, facilitates the designing advanced therapeutic strategies. Here, we present an integration mass spectrometry imaging-based metabolomics lipidomics microarray-based transcriptomics to hierarchically visualize intratumor heterogeneity cell interactions in same gastric cancer sample. Tumor-associated reprogramming is imaged at metabolic-transcriptional levels, maker metabolites, lipids, genes are connected pathways colocalized heterogeneous tissues. Integrated data from multi-omics approaches coherently identify types distributions within complex microenvironment, immune cell-dominated “tumor-normal interface” region where contact adjacent tissues characterized distinct transcriptional signatures significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture heterogeneity, transform metabolism systemic level.

Language: Английский

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Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression

Immunity, Journal Year: 2023, Volume and Issue: 56(8), P. 1825 - 1843.e6

Published: July 13, 2023

Language: Английский

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Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 3, 2024

Abstract Zinc metabolism at the cellular level is critical for many biological processes in body. A key observation disruption of homeostasis, often coinciding with disease progression. As an essential factor maintaining equilibrium, zinc has been increasingly spotlighted context development. Extensive research suggests zinc’s involvement promoting malignancy and invasion cancer cells, despite its low tissue concentration. This led to a growing body literature investigating metabolism, particularly functions transporters storage mechanisms during transportation under control two major transporter families: SLC30 (ZnT) excretion SLC39 (ZIP) intake. Additionally, this element predominantly mediated by metallothioneins (MTs). review consolidates knowledge on signaling underscores potential molecular pathways linking progression, special focus cancer. We also compile summary clinical trials involving ions. Given main localization cell membrane, targeted therapies, including small molecules monoclonal antibodies, offers promising avenues future exploration.

Language: Английский

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Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance

npj Precision Oncology, Journal Year: 2022, Volume and Issue: 6(1)

Published: May 4, 2022

Prostate cancer is characterized by a high degree of heterogeneity, which poses major challenge to precision therapy and drug development. In this review, we discuss how nongenetic factors contribute heterogeneity prostate cancer. We also tumor phenotypic switching related anticancer therapies. Lastly, summarize the challenges targeting environments, emphasize that continued exploration needed in order offer personalized for advanced patients.

Language: Английский

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Tumor-associated macrophages: an effective player of the tumor microenvironment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 16, 2023

Cancer progression is primarily caused by interactions between transformed cells and the components of tumor microenvironment (TME). TAMs (tumor-associated macrophages) make up majority invading immune components, which are further categorized as anti-tumor M1 pro-tumor M2 subtypes. While known to have anti-cancer properties, recognized extend a protective role tumor. As result, manipulates TME in such way that it induces macrophage infiltration switching bias secure its survival. This M2-TAM promotes cancer cell proliferation, neoangiogenesis, lymphangiogenesis, epithelial-to-mesenchymal transition, matrix remodeling for metastatic support, manipulation an immunosuppressive state. additionally promote emergence stem (CSCs), their ability originate, metastasize, relapse into tumors. CSCs also help revealing escape survival strategies during initiation phases. review describes reasons immunotherapy failure and, thereby, devises better impair tumor-TAM crosstalk. study will shed light on understudied TAM-mediated address much-needed holistic approach therapy, encompasses targeting cells, CSCs, all at same time.

Language: Английский

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The hallmarks of cancer immune evasion

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

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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