Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas DOI Creative Commons
Wenshu Tang,

Cario W. S. Lo,

Wei Ma

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 21, 2024

Abstract Background Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within environment remain poorly understood, reliable prognostic markers elusive. Therefore, in-depth exploration (TME) identification predictive are crucial for improving clinical management patients. Results Our analysis single-cell RNA-sequencing data from samples unveiled immunosuppressive role tumor-associated macrophages (TAMs), mediated through intricate interactions with cells lymphocytes. We also discovered heterogeneity TAMs, among which group TAMs named TAM-SPP1 demonstrated significant association Epidermal Growth Factor Receptor ( EGFR ) amplification, impaired T cell response survival Furthermore, by leveraging genomic transcriptomic Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes different constitution status outcomes were identified. Exploiting differences between these subtypes, we developed four-gene-based model. This model displayed strong associations an elevated level could be used predict anti-tumor prognosis in Conclusion findings illuminated mechanisms that shape gliomas, providing novel insights potential therapeutic targets. holds promise predicting immunotherapy assisting more precise risk stratification Graphical abstract

Language: Английский

Angiogenic signaling pathways and anti-angiogenic therapy for cancer DOI Creative Commons

Zhenling Liu,

Huanhuan Chen,

Lili Zheng

et al.

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

Published: May 11, 2023

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- anti-angiogenic molecules, which plays crucial role in tumor growth, invasion, metastasis. With advances molecular cellular biology, biomolecules such as growth factors, chemokines, adhesion factors involved angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules driven treatment to become promising strategy anti-tumor therapy. The most widely used agents include monoclonal antibodies tyrosine kinase inhibitors (TKIs) targeting vascular endothelial factor (VEGF) pathway. However, clinical benefit this modality still limited due several defects adverse events, acquired drug resistance, recurrence, lack validated biomarkers, impel further mechanisms angiogenesis, development multiple drugs combination therapy figure out how improve efficacy. Here, we broadly summarize signaling pathways discuss current challenges We also propose approaches efficacy provide perspective for

Language: Английский

Citations

543
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

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

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

165
A Positive Feedback Loop between Inactive VHL-Triggered Histone Lactylation and PDGFRβ Signaling Drives Clear Cell Renal Cell Carcinoma Progression DOI Creative Commons

Jiefeng Yang,

Li Luo,

Chongyu Zhao

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(8), P. 3470 - 3483

Published: Jan. 1, 2022

Inactive von Hippel-Lindau (VHL) is linked to metabolic reprogramming and plays pivotal roles in the pathogenesis of clear cell renal carcinoma (ccRCC).Here, we identify a previously unknown oncogenic role for inactive VHL actively triggering histone lactylation promote ccRCC progression.In patients with ccRCC, positively correlates presence lactylation, high levels indicates poor patient prognosis.Inactive VHL-triggered contributes progression by activating transcription platelet-derived growth factor receptor β (PDGFRβ).In turn, PDGFRβ signaling shown stimulate thereby forming an positive feedback loop ccRCC.Target correction aberrant represses metastasis vivo.More importantly, combined inhibition significantly reinforces therapeutic efficacy.This work underscores importance facilitating suggests targeting between might provide promising strategy patients.

Language: Английский

Citations

125
A concise review of VEGF, PDGF, FGF, Notch, angiopoietin, and HGF signalling in tumor angiogenesis with a focus on alternative approaches and future directions DOI
Selvaraj Vimalraj

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 221, P. 1428 - 1438

Published: Sept. 17, 2022

Language: Английский

Citations

99
Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies DOI Creative Commons
Changyu Yao,

Shilun Wu,

Jian Kong

et al.

Cancer Biology and Medicine, Journal Year: 2023, Volume and Issue: 20(1), P. 25 - 43

Published: Jan. 12, 2023

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, process formation new blood vessels, required for cancer cells to obtain nutrients and oxygen. HCC a typical hypervascular solid tumor with an aberrant vascular network angiogenesis that contribute its growth, progression, invasion, metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, endothelial growth factor receptor (VEGFR), platelet-derived (PDGFR), are considered effective strategies HCC, particularly advanced HCC. However, because survival benefits conferred by these modest, targets must be identified. Several recent studies have determined underlying molecular mechanisms, including pro-angiogenic factors secreted cells, microenvironment, stem cells. In this review, we summarize roles factors; involvement hepatic stellate tumor-associated macrophages, neutrophils present in microenvironment; regulatory influence on Furthermore, discuss some clinically approved potential novel therapeutic A better understanding mechanisms may lead development more optimized treatment modalities

Language: Английский

Citations

80
New insights about the PDGF/PDGFR signaling pathway as a promising target to develop cancer therapeutic strategies DOI Creative Commons
Pratibha Pandey, Fahad Khan, Tarun Kumar Upadhyay

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114491 - 114491

Published: March 13, 2023

Numerous cancers express platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs). By directly stimulating tumour cells in an autocrine manner or by stromal a paracrine manner, the factor (PDGF)/platelet-derived receptor (PDGFR) pathway is crucial spread of several cancers. To combat hypoxia microenvironment, it encourages angiogenesis. A growing body experimental data shows that PDGFs target malignant cells, vascular to modulate growth, metastasis, microenvironment. medication resistance enhance patient outcomes cancers, targeting PDGF/PDGFR viable therapeutic approach. There have been reports anomalies pathway, including gain function point mutations, activating chromosomal translocations, overexpression amplification As result, has shown signaling effective method for treating cancer. this study will concentrate on regulation system, particular current methods inhibitors used cancer treatment, as well associated advantages side effects.

Language: Английский

Citations

74
Targeting cytokine and chemokine signaling pathways for cancer therapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

Citations

67
Targeting the tumor microenvironment: Potential strategy for cancer therapeutics DOI Creative Commons
Quratulain Babar, Ayesha Saeed, Tanveer A. Tabish

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(6), P. 166746 - 166746

Published: May 7, 2023

Cellular and stromal components including tumor cells, immune mesenchymal cancer-linked fibroblasts, extracellular matrix, constituent microenvironment (TME). TME plays a crucial role in reprogramming initiation, uncontrolled proliferation, invasion metastasis as well response to therapeutic modalities. In recent years targeting the has developed potential strategy for treatment of cancer because its life-threatening functions restricting development modulating responses standard-of-care medicines. Cold atmospheric plasma, oncolytic viral therapy, bacterial nano-vaccine, repurposed pharmaceuticals with combination antiangiogenic drugs, immunotherapies are among most effective therapies directed by that have either been clinically authorized or currently being studied. This article discusses above-mentioned light TME. We also cover problems related TME-targeted therapies, future insights practical uses this rapidly growing field.

Language: Английский

Citations

54
Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets DOI Creative Commons
Zhaoliang Hu,

Xushi Zhao,

Zhonghua Wu

et al.

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

Published: Jan. 3, 2024

Abstract Lymphatic vessels, comprising the secondary circulatory system in human body, play a multifaceted role maintaining homeostasis among various tissues and organs. They are tasked with serious of responsibilities, including regulation lymph absorption transport, orchestration immune surveillance responses. vessel development undergoes series sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into highly specialized lymphatic networks. Lymphangiogenesis, as defined by new vessels sprouting from preexisting vessels/embryonic veins, is main developmental mechanism underlying formation expansion networks an embryo. However, abnormal lymphangiogenesis could be observed many pathological conditions has close relationship progression diseases. Mechanistic studies have revealed set lymphangiogenic factors cascades that may serve potential targets for regulating lymphangiogenesis, further modulate Actually, increasing number clinical trials demonstrated promising interventions showed feasibility currently available treatments future translation. Targeting promoters or inhibitors not only directly regulates but improves efficacy diverse treatments. In conclusion, we present comprehensive overview physiological functions, describe critical involvement multiple Moreover, summarize targeting therapeutic values providing novel perspectives treatment strategy

Language: Английский

Citations

30
A Molecular Perspective on HIF-1α and Angiogenic Stimulator Networks and Their Role in Solid Tumors: An Update DOI Open Access

Anuja Gajanan Magar,

Vivek Kumar Morya, Mi Kyung Kwak

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3313 - 3313

Published: March 14, 2024

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional factor, which plays an important role in cellular reprogramming processes under hypoxic conditions, facilitate solid tumors' progression. HIF-1α directly involved the regulation of angiogenesis, metabolic reprogramming, and extracellular matrix remodeling tumor microenvironment. Therefore, in-depth study on malignancies required to develop novel anti-cancer therapeutics. also critical regulating growth factors, such as vascular endothelial fibroblast platelet-derived network manner. Additionally, it significant progression chemotherapy resistance by variety angiogenic including angiopoietin 1 2, metalloproteinase, erythropoietin, along with energy pathways. this review attempts provide comprehensive insight into angiogenesis pathways tumors.

Language: Английский

Citations

26