2026-10-09T17:39:41Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34018407 2026-09-28T20:38:53Z category_24778 item_type_12 month_year_09_2026

Dual Fuel Modulation (DFM): A Precision Metabolic Platform for Exploiting Ferroptotic Vulnerability and Metabolic Plasticity in Glioblastoma Mustafa Al-wasabi (24553704) Cancer cell biology SLC7A11/GPX4 axis Metabolic plasticity cancer metabolism ferroptosis caused Glioblastoma Cell Lines Glioblastoma <p dir="ltr">Glioblastoma (GBM) is characterized by profound metabolic heterogeneity and plasticity, enabling tumor-cell populations to adapt to energetic, oxidative, and therapeutic stress. Dual Fuel Modulation (DFM) is proposed as a hypothesis-generating metabolic framework designed to investigate whether this adaptive capacity can be converted into a therapeutic vulnerability through coordinated perturbation of interconnected metabolic systems.</p><p dir="ltr"><br></p><p dir="ltr">Rather than assuming that GBM is uniformly dependent on a single metabolic pathway, DFM proposes that selected tumor phenotypes may become vulnerable when glycolytic flux, cystine-dependent antioxidant capacity, membrane lipid susceptibility to peroxidation, and compensatory mitochondrial metabolism are challenged within an experimentally defined therapeutic window. The framework integrates four conceptual pressures: controlled glycolytic modulation; impairment of System Xc⁻-dependent cystine utilization and glutathione homeostasis; enhancement of lipid-peroxidation susceptibility through selected polyunsaturated fatty acids (PUFAs); and partial modulation of mitochondrial oxidative phosphorylation to reduce metabolic compensation.</p><p><br></p><p dir="ltr">DFM remains a testable systems-level hypothesis rather than a validated therapeutic regimen. Its principal scientific question is whether coordinated metabolic pressure can produce reproducible, phenotype-dependent ferroptotic vulnerability in GBM while maintaining a meaningful differential effect between tumor and normal neural tissue.</p> 2026-09-28T20:38:53Z Text Preprint 10.6084/m9.figshare.34018407.v1 https://figshare.com/articles/preprint/Dual_Fuel_Modulation_DFM_A_Precision_Metabolic_Platform_for_Exploiting_Ferroptotic_Vulnerability_and_Metabolic_Plasticity_in_Glioblastoma/34018407 CC BY 4.0