Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, 110, Taiwan.
International Master Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, 110, Taiwan.
Lipids Health Dis. 2023 Aug 3;22(1):114. doi: 10.1186/s12944-023-01881-5.
Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM.
胶质母细胞瘤（GBM）是一种具有高度侵袭性和致命性的脑肿瘤，治疗选择有限，如化疗药物替莫唑胺（TMZ）。然而，许多 GBM 肿瘤对 TMZ 产生耐药性，这是有效治疗的主要障碍。最近，脂质代谢失调已成为导致 GBM 对 TMZ 耐药的一个重要因素。脂质代谢失调是癌症的一个标志，脂质代谢的改变与肿瘤生物学的多个方面有关，包括增殖、迁移和对治疗的耐药性。在这篇综述中，我们旨在总结 TMZ 耐药性 GBM 中脂质代谢的最新知识，包括参与脂质合成、摄取和利用的关键代谢物和蛋白质，以及代谢组学在研究 GBM 中脂质代谢方面的最新进展。我们还讨论了将脂质代谢作为新的治疗干预靶点的潜力。最后，我们强调了为临床应用开发这些干预措施所面临的挑战和机遇，以及进一步研究以充分了解脂质代谢在 GBM 对 TMZ 耐药性中的作用的必要性。我们的综述表明，靶向失调的脂质代谢可能是克服 TMZ 耐药性和改善 GBM 患者预后的一种有前途的方法。
