Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology Pub Date : 2025-01-26 DOI:10.1016/j.jbo.2025.100660

Zhiyang Yin , Guanlu Shen , Minjie Fan , Pengfei Zheng

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引用次数: 0

Abstract

Osteosarcoma is a common bone tumor in adolescents, which is characterized by lipid metabolism disorders and plays a key role in tumorigenesis and disease progression. Ferroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. This review provides an in-depth analysis of the complex relationship between lipid metabolic reprogramming and associated ferroptosis in OS from the perspective of metabolic enzymes and metabolites. We discussed the molecular basis of lipid uptake, synthesis, storage, lipolysis, and the tumor microenvironment, as well as their significance in OS development. Key enzymes such as adenosine triphosphate-citrate lyase (ACLY), acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1) are overexpressed in OS and associated with poor prognosis.

Based on specific changes in metabolic processes, this review highlights potential therapeutic targets in the lipid metabolism and ferroptosis pathways, and in particular the HMG-CoA reductase inhibitor simvastatin has shown potential in inducing apoptosis and inhibiting OS metastasis. Targeting these pathways provides new strategies for the treatment of OS. However, challenges such as the complexity of drug development and metabolic interactions must be overcome. A comprehensive understanding of the interplay between dysregulation of lipid metabolism and ferroptosis is essential for the development of innovative and effective therapies for OS, with the ultimate goal of improving patient outcomes.

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来源期刊

Journal of Bone Oncology ONCOLOGY-

CiteScore

7.20

自引率

2.90%

发文量

审稿时长

34 days

期刊介绍： The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer. As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject. The areas covered by the journal include: Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment) Preclinical models of metastasis Bone microenvironment in cancer (stem cell, bone cell and cancer interactions) Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics) Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management) Bone imaging (clinical and animal, skeletal interventional radiology) Bone biomarkers (clinical and translational applications) Radiotherapy and radio-isotopes Skeletal complications Bone pain (mechanisms and management) Orthopaedic cancer surgery Primary bone tumours Clinical guidelines Multidisciplinary care Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.