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oai:figshare.com:article/34018461 2026-09-28T20:55:23Z category_24778 item_type_12 month_year_09_2026

Candidate Adaptive Resistance Mechanisms to Dual Fuel Modulation (DFM) in Glioblastoma: A Molecular and Epitranscriptomic Perspective Mustafa Al-wasabi (24553704) Cancer cell biology epitranscriptomics ). alkbh5 mrna Nrf2 agonist atf4-mediated Adaptive ResistanceThe glioblastoma c6 cell <p><br></p><p dir="ltr">Dual Fuel Modulation (DFM) proposes that coordinated metabolic pressure may increase ferroptotic vulnerability in selected glioblastoma (GBM) phenotypes. However, an important unanswered question is how surviving tumor cells adapt to this stress and restore metabolic and redox homeostasis. This companion hypothesis proposes that DFM-induced metabolic stress may activate layered resistance programs involving transcriptional, chromatin, epitranscriptomic, and non-coding RNA regulation. Four candidate adaptive axes are considered: ATF4/NRF2-associated stress responses; miRNA–lncRNA regulation potentially preserving SLC7A11/GPX4 activity; metabolically influenced chromatin remodeling involving acetyl-CoA, H3K27ac, and BRD4-associated transcription; and a DAMER–ALKBH5–ATF4 epitranscriptomic mechanism previously implicated in nutrient-stress adaptation in cancer models. These mechanisms are not assumed to operate universally or simultaneously. Instead, they are proposed as candidate resistance programs that may emerge in distinct GBM metabolic states. The central hypothesis is that metabolic and ferroptotic stress generated by DFM may activate one or more of these adaptive circuits, allowing a subset of surviving cells to transition from transient stress into a more stable ferroptosis-resistant state. Until experimentally validated, all proposed axes remain testable mechanistic hypotheses.</p> 2026-09-28T20:55:23Z Text Preprint 10.6084/m9.figshare.34018461.v1 https://figshare.com/articles/preprint/Candidate_Adaptive_Resistance_Mechanisms_to_Dual_Fuel_Modulation_DFM_in_Glioblastoma_A_Molecular_and_Epitranscriptomic_Perspective/34018461 CC BY 4.0