Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications DOI Creative Commons

Youssef Elshimy,

Ala’a Aldeen Alkhatib,

Bilal Atassi

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1160 - 1160

Published: May 10, 2025

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides comprehensive analysis the complex interactions between tumor cells bone microenvironment, emphasizing relevance “seed soil” hypothesis, RANK/RANKL/OPG signaling axis, Wnt pathways that collectively drive metastatic progression. The molecular cellular mechanisms underlying formation osteolytic osteoblastic lesions are examined detail, with particular focus on their implications for associated breast, prostate, lung, other cancers. A central component this is categorization pathological biomarkers into four types: diagnostic, prognostic, predictive, monitoring. We provide evaluation circulating (CTCs), turnover markers (such as TRACP-5b CTX), imaging (including PET/CT MRI), novel genomic signatures. These offer valuable insights early detection, enhanced risk stratification, optimized therapeutic decision-making. Furthermore, emerging strategies immunotherapy bone-targeted treatments discussed, highlighting potential biomarker-guided precision medicine to enhance personalized care. distinctiveness lies its integrative approach, combining fundamental pathophysiological latest developments biomarker discovery innovation. By synthesizing evidence across various cancer types categories, we cohesive framework aimed at advancing both scientific understanding clinical management metastases.

Language: Английский

MMP28 recruits M2-type tumor-associated macrophages through MAPK/JNK signaling pathway-dependent cytokine secretion to promote the malignant progression of pancreatic cancer DOI Creative Commons

Shi Dong,

Xin Li, Chen Zhou

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 19, 2025

Abstract Background Crosstalk between pancreatic cancer cells and tumor-associated macrophages (TAMs) is a critical driver of malignant progression, plays an important role in the low response rate to immunotherapy patients with for cancer. Although it known that induce TAM infiltration M2 polarization, underlying mechanisms remain elusive. Herein, we identified matrix metalloproteinase 28 (MMP28), highly expressed protein, as key regulator this process. Methods Immunohistochemical staining qRT-PCR were used validate MMP28 potential marker prognosis We evaluated tumor-promoting effect vitro CCK-8, Transwell, EdU assay Western blotting explored mechanism MMP28-induced polarization TAMs coculture system, immunofluorescence flow cytometry. A subcutaneous graft tumor model was constructed assess its ability infiltration. Results The relevant results study revealed strong correlation expression infiltration, predominance M2-polarized tissues. Mechanistic investigations demonstrated promotes secretion multiple cytokines, including IL-8 VEGFA through activation MAPK/JNK signaling pathway. These cytokines act potent chemoattractants polarizing factors TAMs. Additionally, discovered interaction ANXA2, which contributes regulation recruitment polarization. In vivo studies confirmed growth Depletion macrophages, inhibition JNK, or neutralization significantly suppressed progression. Transcriptomic analysis suggested by modulating amino acid metabolism. Conclusions Collectively, our findings elucidate novel manipulate microenvironment MMP28-dependent cytokine secretion, promoting highlight promising therapeutic target Graphical Schematic overview migration High levels promote mediating phosphorylation signalling pathway then recruiting subsequently metabolism alterations binding receptors on TAMs, ultimately phenotype. addition, ANXA2 increases MMP28-mediated interacting MMP28.

Language: Английский

Citations

1
Lipid metabolism dysregulation for bone metastasis and its prevention DOI

Jyoti Poswal,

Chandi C. Mandal

Expert Review of Anticancer Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Bone metastasis often develops in advanced malignancies. Lipid metabolic dysregulation might play pivotal role cancer progression and subsequent deterioration of bone health at metastatic condition. In-depth understanding lipid reprogramming metastasized cells other stromal including marrow adipocyte (BMA) is an urgent need to develop effective therapy. This paper emphasizes providing overview multifaceted dysregulated lipids BMA association with by utilizing search terms metabolism, PubMed. study extends address mechanism linked metabolism various crucial genes (e.g. CSF-1, RANKL, NFkB NFATc1) involved metastasis. review examines therapeutic strategies targeting offer potential avenues disrupt lipid-driven On condition, molecules especially not only favors but also potentiate within cells. Distinct lipid-metabolism associated may act as biomarker, these challenging task for specific treatment. Curbing function resorption controlling drugs statins, omega-3 FA metformin) provide additional support curtail lipid-associated

Language: Английский

Citations

0
The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance DOI Open Access
Ahmad Dawalibi, Mohamad Bakir,

Khalid S. Mohammad

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis quality of life. This review article delves into the genetic epigenetic mechanisms underpinning drug resistance bone metastases, a key challenge effective cancer treatment. The development can manifest as either intrinsic or acquired, with heterogeneity playing pivotal role. Intrinsic is often due to pre-existing mutations, while acquired evolves through alterations during These include mutations driver genes like TP53 RB1, modifications such DNA methylation histone changes, pathway alterations, involving RANK-RANKL signaling PI3K/AKT/mTOR cascade. Recent studies underline significance tumor microenvironment fostering resistance, components cancer-associated fibroblasts hypoxia crucial roles. interactions between metastatic cells facilitate survival proliferation drug-resistant clones. highlights necessity understanding these complex develop targeted therapies that overcome improve treatment outcomes. Current therapeutic strategies future directions are discussed, emphasizing integration genomic profiling interventions managing metastases. evolving landscape research, including application next-generation sequencing CRISPR technology, offers promising avenues for novel more strategies. comprehensive exploration aims provide insights molecular intricacies paving way improved clinical management patient care.

Language: Английский

Citations

0
Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications DOI Creative Commons

Youssef Elshimy,

Ala’a Aldeen Alkhatib,

Bilal Atassi

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1160 - 1160

Published: May 10, 2025

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides comprehensive analysis the complex interactions between tumor cells bone microenvironment, emphasizing relevance “seed soil” hypothesis, RANK/RANKL/OPG signaling axis, Wnt pathways that collectively drive metastatic progression. The molecular cellular mechanisms underlying formation osteolytic osteoblastic lesions are examined detail, with particular focus on their implications for associated breast, prostate, lung, other cancers. A central component this is categorization pathological biomarkers into four types: diagnostic, prognostic, predictive, monitoring. We provide evaluation circulating (CTCs), turnover markers (such as TRACP-5b CTX), imaging (including PET/CT MRI), novel genomic signatures. These offer valuable insights early detection, enhanced risk stratification, optimized therapeutic decision-making. Furthermore, emerging strategies immunotherapy bone-targeted treatments discussed, highlighting potential biomarker-guided precision medicine to enhance personalized care. distinctiveness lies its integrative approach, combining fundamental pathophysiological latest developments biomarker discovery innovation. By synthesizing evidence across various cancer types categories, we cohesive framework aimed at advancing both scientific understanding clinical management metastases.

Language: Английский

Citations

0