Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments DOI Creative Commons
Konstantinos Avgoustakis, Athina Angelopoulou

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(2), P. 179 - 179

Published: Jan. 26, 2024

Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays crucial role in the clinical therapeutic outcome conventional treatments innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering challenges tumor microenvironment (TME), respect effective drug accumulation activity at site. The main focus is overcome obstacles abnormal vasculature, dense stroma, extracellular matrix, hypoxia, pH gradient acidosis. In this endeavor, nanomedicines that targeting distinct features TME flourished; these aim increase site specificity achieve deep penetration. Recently, research focused on immune reprograming order promote suppression cancer stem cells prevention metastasis. Thereby, several nanomedicine therapeutics which shown promise preclinical studies entered trials or already practice. Various novel strategies were employed trials. Among them, based biomaterials show improving efficacy, reducing side effects, promoting synergistic for responsive targeting. review, we mechanisms response solid tumors. We describe take advantage biomaterials’ properties exploit posed by TME. development such systems has significantly advanced application combinational therapies immunotherapies improved anticancer effectiveness.

Language: Английский

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials DOI Creative Commons
Hao Zhang,

Xinghai Yue,

Zhe Chen

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

Citations

159
Unveiling the mechanisms and challenges of cancer drug resistance DOI Creative Commons
Sameer Ullah Khan, Kaneez Fatima,

Shariqa Aisha

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

Citations

107
Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment DOI Creative Commons

Chenxi Ma,

Chengzhe Yang,

Ai Peng

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 13, 2023

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays crucial role in remodeling the tumor microenvironment (TME). Here, through integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups CAFs described their distribution characteristics. Additionally, RNA sequencing (scRNA-seq) from three additional types two newly generated scRNA-seq datasets rare namely epithelial-myoepithelial carcinoma (EMC) mucoepidermoid (MEC), expanded our understanding CAF heterogeneity. Cell-cell interaction conducted within context highlighted pivotal roles matrix (mCAFs) angiogenesis inflammatory (iCAFs) shaping immunosuppressive microenvironment. In patients with breast (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity facilitating proliferation, promoting epithelial-mesenchymal transition (EMT), contributing to establishment an Furthermore, scoring system based on showed significant correlation immune therapy response melanoma patients. Lastly, provided web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for research community investigate pan-cancer.

Language: Английский

Citations

104
Application of radiomics-based multiomics combinations in the tumor microenvironment and cancer prognosis DOI Creative Commons

Wendi Kang,

Xiang Qiu,

Yingen Luo

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 6, 2023

Abstract The advent of immunotherapy, a groundbreaking advancement in cancer treatment, has given rise to the prominence tumor microenvironment (TME) as critical area research. clinical implications an improved understanding TME are significant and far-reaching. Radiomics been increasingly utilized comprehensive assessment prognosis. Similarly, pathomics, which is based on pathological images, can offer additional insights into panoramic view microscopic information tumors. combination pathomics radiomics revolutionized concept “digital biopsy”. As genomics transcriptomics continue evolve, integrating with genomic transcriptomic datasets further heterogeneity establish correlations biological significance. Therefore, synergistic analysis digital image features (radiomics, pathomics) genetic phenotypes (genomics) comprehensively decode characterize well predict This review presents summary research important biomarkers for predicting TME, emphasizing interplay between radiomics, genomics, transcriptomics, application multiomics decoding Finally, we discuss challenges opportunities In conclusion, this highlights crucial role associations combined promising direction substantial significance value evaluation prognosis assessment.

Language: Английский

Citations

50
Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers DOI Creative Commons
Yuanfang Li, Baiwei Zhao,

Juzheng Peng

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101042 - 101042

Published: Jan. 4, 2024

Drug resistance in cancer remains a major challenge oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as critical player development drug cells. This comprehensive review explores intricate relationship between NF-κB and cancer. We delve into molecular mechanisms through which activation contributes to against chemotherapeutic agents, targeted therapies, immunotherapies. Additionally, we discuss potential strategies overcome this by targeting signaling, such small molecule inhibitors combination therapies. Understanding multifaceted interactions is crucial for more effective strategies. By dissecting complex network NF-κB, hope shed light on novel therapeutic approaches that can enhance outcomes, ultimately improving prognosis patients. aims provide overview current state knowledge its role resistance, offering insights may guide future research interventions fight

Language: Английский

Citations

37
An Engineered Nanoplatform with Tropism Toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy DOI
Zheng Wang, Fangman Chen, Yi Cao

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(32)

Published: May 7, 2024

Combining radiotherapy with immune checkpoint blockade therapy offers a promising approach to treat glioblastoma multiforme (GBM), yet challenges such as limited effectiveness and immune-related adverse events (irAEs) persist. These issues are largely due the failure in targeting immunomodulators directly tumor microenvironment. To address this, biomimetic nanoplatform that combines genetically modified mesenchymal stem cell (MSC) membrane bioactive nanoparticle core for chemokine-directed radioimmunotherapy of GBM is developed. The CC chemokine receptor 2 (CCR2)-overexpressing MSC acts tactical tentacle achieve radiation-induced tropism toward abundant (CC motif) ligand (CCL2) irradiated gliomas. core, comprising diselenide-bridged mesoporous silica nanoparticles (MSNs) PD-L1 antibodies (αPD-L1), enables X-ray-responsive drug release radiosensitization. In two murine models orthotopic tumors, this reinvigorated immunogenic death, augmented efficacy specificity radioimmunotherapy, reduced occurrence irAEs. This study suggests strategy targeted delivery, presents potent enhances safety radio-immunotherapy.

Language: Английский

Citations

23
Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology DOI Creative Commons
Kamelia Hristova‐Panusheva, Charilaos Xenodochidis, Milena Georgieva

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 677 - 677

Published: May 24, 2024

Nanotechnology has emerged as a transformative force in oncology, facilitating advancements site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cells represents pivotal breakthrough, allowing the precise interventions. These cancer-cell-targeted operate within intricate milieu tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides contemporary perspective on precision medicine underscores critical role nanotechnology advancing It explores categorization nanoparticle types, distinguishing between organic inorganic variants, examines significance delivery anticancer drugs. Current insights into strategies for developing actively across various types are also provided, thus addressing relevant challenges associated with drug barriers. Promising future directions nanomedicine approaches delivered, emphasising imperative continued optimization nanocarriers medicine. discussion translational research’s need enhance patients’ outcomes by refining nanocarrier technologies nanotechnology-driven, therapy.

Language: Английский

Citations

20
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

19
Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects DOI Creative Commons
Zhipeng Cao,

Sadia Quazi,

Sakshi Arora

et al.

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 9, 2025

Abstract Research into cancer treatment has been mainly focused on developing therapies to directly target cells. Over the past decade, extensive studies have revealed critical roles of tumour microenvironment (TME) in initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) emerged as one primary contributors shaping TME, creating a favourable environment for development. Many preclinical identified promising targets CAFs, demonstrating remarkable efficacy some CAF-targeted treatments models. Encouraged by these compelling findings, therapeutic strategies now advanced clinical evaluation. We aim provide comprehensive review relevant subjects including CAF-related markers targets, their multifaceted roles, current landscape ongoing trials. This knowledge can guide future research CAFs advocate investigations targeting CAFs.

Language: Английский

Citations

9
A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer DOI Creative Commons

Qianhe Ren,

Pengpeng Zhang, Xiao Zhang

et al.

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

Published: May 29, 2023

Background Current paradigms of anti-tumor therapies are not qualified to evacuate the malignancy ascribing cancer stroma’s functions in accelerating tumor relapse and therapeutic resistance. Cancer-associated fibroblasts (CAFs) has been identified significantly correlated with progression therapy Thus, we aimed probe into CAFs characteristics esophageal squamous (ESCC) construct a risk signature based on predict prognosis ESCC patients. Methods The GEO database provided single-cell RNA sequencing (scRNA-seq) data. TCGA databases were used obtain bulk RNA-seq data microarray ESCC, respectively. CAF clusters from scRNA-seq using Seurat R package. CAF-related prognostic genes subsequently univariate Cox regression analysis. A was constructed Lasso regression. Then, nomogram model clinicopathological developed. Consensus clustering conducted explore heterogeneity ESCC. Finally, PCR utilized validate that hub play Results Six data, three which had associations. total 642 found be pool 17080 DEGs, 9 selected generate signature, mainly involved 10 pathways such as NRF1, MYC, TGF-Beta. stromal immune scores, well some cells. Multivariate analysis demonstrated an independent factor for its potential predicting immunotherapeutic outcomes confirmed. novel integrating CAF-based clinical stage developed, exhibited favorable predictability reliability prediction. consensus further confirmed Conclusion can effectively predicted by signatures, comprehensive characterization may aid interpreting response immunotherapy offer new strategies treatment.

Language: Английский

Citations

41