Drug resistance and tumor immune microenvironment: An overview of current understandings (Review) DOI Creative Commons
Yan Liu, Jun Liang, Yanping Zhang

et al.

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 65(4)

Published: Aug. 30, 2024

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis local recurrence. immune microenvironment (TME) consists cells, cytokines immunomodulators, collectively they influence the response treatment. Epigenetic changes including DNA methylation histone modification, as well increased exportation have been reported contribute development in cancers. In past few years, majority studies on tumors only focused progression from mechanistic standpoint; examined whether TME can also affect growth resistance. Recently, emerging evidence raised more concerns regarding role present review, it was discussed how suppressive adapts characterized by cooperation cytokines, stromal cells extracellular matrix. Furthermore, reviewed these immunological or metabolic alter immuno‑surveillance thus facilitate addition, potential targets developing novel therapeutic strategies improve individualized therapy treatment were revealed.

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

Amino acid metabolism in tumor biology and therapy DOI Creative Commons
Jie Chen,

Likun Cui,

Shaoteng Lu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 13, 2024

Abstract Amino acid metabolism plays important roles in tumor biology and therapy. Accumulating evidence has shown that amino acids contribute to tumorigenesis immunity by acting as nutrients, signaling molecules, could also regulate gene transcription epigenetic modification. Therefore, targeting will provide new ideas for treatment become an therapeutic approach after surgery, radiotherapy, chemotherapy. In this review, we systematically summarize the recent progress of malignancy their interaction with signal pathways well effect on microenvironment Collectively, highlight potential application future expectation.

Language: Английский

Citations

72

cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment DOI Creative Commons
Hongying Zhang, Yongliang Liu,

Jieya Liu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 17, 2024

Cancer is a complex disease resulting from abnormal cell growth that induced by number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells angiogenesis, plays critical role in progression. Cyclic adenosine monophosphate (cAMP) second messenger has pleiotropic effects on the TME. downstream effectors cAMP include cAMP-dependent protein kinase (PKA), exchange activated (EPAC) ion channels. While can activate PKA or EPAC promote cancer growth, it also inhibit proliferation survival context- type-dependent manner. Tumor-associated stromal cells, such as CAF release cytokines factors either stimulate production within Recent studies have shown targeting signaling TME therapeutic benefits cancer. Small-molecule agents adenylate cyclase been to growth. In addition, cAMP-elevating agents, forskolin, not only induce death, but directly some types. this review, we summarize current understanding biology immunology discuss basis for its context-dependent dual oncogenesis. Understanding precise mechanisms interact will be development effective therapies. Future aimed at investigating cAMP-cancer axis regulation may provide new insights into underlying tumorigenesis lead novel strategies.

Language: Английский

Citations

40

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment DOI Creative Commons

Shiming Tan,

Yiqing Yang, Wenjuan Yang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: March 10, 2023

Metabolic reprogramming is one of the hallmarks cancer. As nutrients are scarce in tumor microenvironment (TME), cells adopt multiple metabolic adaptations to meet their growth requirements. not only present cells, but exosomal cargos mediates intercellular communication between and non-tumor TME, inducing remodeling create an outpost microvascular enrichment immune escape. Here, we highlight composition characteristics meanwhile summarize components corresponding sorting mode. Functionally, these cargos-mediated improves "soil" for metastasis. Moreover, discuss abnormal metabolism targeted by its potential antitumor therapy. In conclusion, this review updates current role TME enriches future application scenarios exosomes.

Language: Английский

Citations

42

Cancer-associated fibroblasts: Key criminals of tumor pre-metastatic niche DOI Creative Commons
Guozhang Dong, Peng Chen,

Youtao Xu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 566, P. 216234 - 216234

Published: May 24, 2023

Cancer-associated fibroblasts (CAFs) are abundant and important components of the tumour mesenchyme, have been extensively studied for their role in primary tumours. CAFs provide biomechanical support cells play key roles immunosuppression metastasis. can promote epithelial-mesenchymal transition (EMT) by secreting extracellular vesicles (EVs), increasing adhesion to cells, remodelling matrix (ECM) tumour, changing its mechanical stiffness, which provides a pathway Moreover, form cell clusters with circulating (CTCs) help them resist blood shear forces achieve colonisation distant host organs. Recent studies revealed pre-metastatic niche (PMN) formation prevention. In this review, we discuss PMN therapeutic interventions targeting prevent

Language: Английский

Citations

35

The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism DOI Creative Commons

Kegan Zhu,

Jiayu Yang, Yuehong Zhu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(10)

Published: Oct. 30, 2023

Lymph node metastasis (LNM) is the prominent route of gastric cancer dissemination, and usually leads to tumor progression a dismal prognosis cancer. Although exosomal lncRNAs have been reported be involved in development, whether secreted can encode peptides recipient cells remains unknown. Here, we identified an lncRNA (lncAKR1C2) that was clinically correlated with lymph VEGFC-independent manner. Exo-lncAKR1C2 from demonstrated enhance tube formation migration lymphatic endothelial cells, facilitate lymphangiogenesis vivo. By comparing metabolic characteristics LN metastases primary focuses, found displayed higher lipid activity. Moreover, exo-lncAKR1C2 encodes microprotein (pep-AKR1C2) promotes CPT1A expression by regulating YAP phosphorylation, leading enhanced fatty acid oxidation (FAO) ATP production. These findings highlight novel mechanism LNM suggest encoded lncAKR1C2 serves as therapeutic target for advanced

Language: Английский

Citations

26

Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects DOI Creative Commons
Yingxue Liu, Xiaoyan Zhang, Wenchao Gu

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Tumor metastasis represents a stepwise progression and stands as principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in metastasis. Review This review systematically explores CAFs at eight critical stages tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, 8) premetastatic niche (PMN) formation. Additionally, we provide compendium extant strategies aimed targeting therapy. Key Scientific Concepts delineates structured framework interplay between while furnishing insights potential therapeutic developments. It contributes to deeper understanding TME, facilitating utilization CAF-targeting therapies anti-metastatic approaches.

Language: Английский

Citations

17

Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution DOI Creative Commons
Fusheng Zhang, Yongsu Ma, Dongqi Li

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 2, 2024

Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into intrinsic oncogenic mechanisms of tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) metabolic regulates progression through numerous biological activities, including immunosuppression, chronic inflammation, ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted mediators released via CAFs multiple immune cells collectively thereby inducing pre-metastatic formation, ultimately driving a vicious cycle proliferation metastasis. This review comprehensively explores process regulation dynamic evolution tumor-adapted TME, particular focus on by which promote Existing findings confirm components act cooperatively accelerate events. The potential applications challenges targeted therapies based clinical setting are further discussed context advancing related CAFs.

Language: Английский

Citations

16

Exosomal ncRNAs in liquid biopsies for lung cancer DOI
Md Sadique Hussain, Gaurav Gupta, Nehmat Ghaboura

et al.

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 565, P. 119983 - 119983

Published: Oct. 3, 2024

Language: Английский

Citations

16

Liquid biopsy in lung cancer DOI
Lan Li, Haixia Jiang, Bingjie Zeng

et al.

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 554, P. 117757 - 117757

Published: Jan. 4, 2024

Language: Английский

Citations

15