Dysregulated lipid metabolism in TMZ-resistant glioblastoma: pathways, proteins, metabolites and therapeutic opportunities

• Published in: Lipids in health and disease Vol. 22; no. 1; p. 114
• Main Authors: Kao, Tzu-Jen, Lin, Chien-Liang, Yang, Wen-Bin, Li, Hao-Yi, Hsu, Tsung-I
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.08.2023; BioMed Central; BMC
• Subjects: Antineoplastic Agents, Alkylating - pharmacology; Antineoplastic Agents, Alkylating - therapeutic use; Apoptosis; Biosynthesis; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Cancer therapies; Cell cycle; Cell division; Cell growth; Cell Line, Tumor; Chemotherapy; Development and progression; DNA methylation; Drug resistance; Drug Resistance, Neoplasm; Drug therapy; Enzymes; Epigenetics; Fatty acids; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma multiforme; Glucose; Health aspects; Humans; Lipid Metabolism; Lipids; Medical prognosis; Metabolism; Metabolites; Metabolomics; Physiological aspects; Proteins; Radiation therapy; Remission (Medicine); Review; Temozolomide; Temozolomide - pharmacology; Temozolomide - therapeutic use; Therapeutic applications; Tumors; Xenograft Model Antitumor Assays; China
• ISSN: 1476-511X; 1476-511X
• 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.