Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Galina V BeznusenkoIFOM ETS-The AIRC Institute of Molecular Oncology, Milan, Italy.
Mara-Camelia RusuMax-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany.ORCID 0000-0002-8369-3580
Francesco FaveroDepartment of Translational Medicine, Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, Novara 28100, Italy.ORCID 0000-0003-3482-8335
Davide CoràDepartment of Translational Medicine, Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, Novara 28100, Italy.
Domenico A SilvestrisUnit of Genetics and Epigenetic of Pediatric Cancer, Oncohaematology Department, IRCCS Ospedale Pediatrico Bambino Gesù, Viale di San Paolo 15, Rome 00146, Italy.
Angela GalloUnit of Genetics and Epigenetic of Pediatric Cancer, Oncohaematology Department, IRCCS Ospedale Pediatrico Bambino Gesù, Viale di San Paolo 15, Rome 00146, Italy.ORCID 0000-0003-0297-1807
Valentina GambinoDepartment of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan 20139, Italy.
Fabio AlfieriDepartment of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan 20139, Italy.ORCID 0000-0001-7173-0105
Sara GandiniDepartment of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan 20139, Italy.ORCID 0000-0002-1348-4548
Matthias J SchmittMax-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany.ORCID 0000-0001-8296-5858
Gaetano GargiuloMax-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany.ORCID 0000-0001-5414-4251
Roberta NoberiniDepartment of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan 20139, Italy.ORCID 0000-0002-7267-1079
Tiziana BonaldiDepartment of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan 20139, Italy.ORCID 0000-0003-3556-1265
Giuliana PelicciDepartment of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan 20139, Italy.ORCID 0000-0003-0986-8255
Funding
No grant is acknowledged in the PubMed record.
6 · The paper itself
Abstract
Lysine-specific histone demethylase 1A (LSD1) is an epigenetic regulator involved in various biological processes, including metabolic pathways. We demonstrated the therapeutic potential of its pharmacological inhibition in glioblastoma using DDP_38003 (LSD1i), which selectively targets tumor-initiating cells (TICs) by hampering their adaptability to stress. Through biological, metabolic, and omic approaches, we now show that LSD1i acts as an endoplasmic reticulum (ER) stressor, activating the integrated stress response and altering mitochondrial structure and function. These effects impair TICs' oxidative metabolism and generate reactive oxygen species, further amplifying cellular stress. LSD1i also impairs TICs' glycolytic activity, causing their metabolic decline. TICs with enhanced glycolysis benefit from LSD1-directed therapy. Conversely, metabolically silent TICs mantain ER and mitochondrial homeostasis, adapting to stress conditions, including LSD1i treatment. A dropout short hairpin RNA screening identifies postglycosylphosphatidylinositol attachment to proteins inositol deacylase 1 (PGAP1) as a mediator of resistance to LSD1i. Disruptions in ER and mitochondrial balance holds promise for improving LSD1-targeted therapy efficacy and overcoming treatment resistance.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
Metabolic traits shape responses to LSD1-directed therapy in glioblastoma tumor-initiating cells. · full record | Socratic