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. 2023 Jul 24;129(5):811–818. doi: 10.1038/s41416-023-02356-1

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Mechanism of action of 2-OHOA. (1) 2-OHOA regulates the cell membrane composition by both direct incorporation into the lipid bilayer and regulation of important lipid metabolism enzymes, such as SMS-1, stearyl CoA desaturase 1 (SCD1), phospholipases 1 and 2 (PLA1/2), which regulate the levels and types of sphingolipids (SLs) and phospholipids (PLs). (2) Among other structural effects on the lipid bilayer, these changes in lipid composition regulate the raft-to-nonraft lipid balance, which causes translocation of numerous proteins from or to the membrane (e.g., PKC and Ras). (3) The presence or absence of peripheral membrane signalling proteins triggers or hampers, respectively, important signalling cascades. (4) These signalling cascades control glioma cell’s physiology, inducing unfolded protein response (UPR), endoplasmic reticulum (ER) stress, cell cycle arrest, cell differentiation, oxidative phosphorylation uncoupling, and eventually programmed cell death (autophagy). b Clinical trial scheme: Dose escalation had a 3 + 3 scheme. All cohorts received the indicated daily doses in two oral administrations, except those cohorts receiving 12,000 mg/d, which were administered TID (4000 mg per dose).