bims-medica 2025-08-10 papers

bims-medica

Biomed News

on Metabolism and diet in cancer

Issue of 2025–08–10
25 papers selected by
Brett Chrest, Wake Forest University

Distinct proteomic and acylproteomic adaptations to succinate dehydrogenase loss in two cell contexts.
Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control.
Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.
The effects of dietary fat on gut microbial composition and function in a mouse model of ovarian cancer.
Ketogenic diet in the management of disease.
Alanine Catabolism as a Targetable Vulnerability for MYC-Driven Liver Cancer.
Impact of ketogenic diets on cancer patient outcomes: a systematic review and meta-analysis.
Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.
Cysteine Oxidation of a Redox Hub within Complex I can Facilitate Electron Transport Chain Supercomplex Formation.
Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice.
PPARγ-induced upregulation of fatty acid metabolism confers resistance to venetoclax and decitabine therapy in AML.
Donor-specific response of visceral adipocytes differentiated from human adipose-derived mesenchymal stem cells to branched-chain alpha-keto acid (BCKA) dehydrogenase activation.
Role of metabolomic changes in diagnosis and assessment of treatment response in acute myeloid leukemia.
Assessing cellular metabolic dynamics with NAD(P)H fluorescence polarization imaging.
ATP allosterically regulates an acyl-CoA oxidase.
Protocol for measuring mitochondrial respiratory capacity from buccal cell swabs.
Differential Bioenergetic Profile of Human Glioblastoma following Transplantation of Myocyte-derived Mitochondria.
OPPORTUNITIES AND CHALLENGES FOR TARGETING CANCER METABOLISM.
Age-related declines in mitochondrial Prdx6 contribute to dysregulated muscle bioenergetics.
Clinical and translational study of ivosidenib plus nivolumab in advanced solid tumors harboring IDH1 mutations.
Inhibiting the RNA helicase DDX3X in Burkitt lymphoma induces oxydative stress and impedes tumor progression in xenografts.
Alpha-ketoglutarate supplementation differently modifies hematological parameters and oxidative stress in mice fed a standard diet and high-fat high-fructose diet.
Safety of venetoclax in real-world experience: data from the French national database of pharmacovigilance through all indications in hematological malignancies over 5 years.
Asparagine synthetase modulates glutaminase inhibitor sensitivity through metabolic reprogramming and serves as a prognostic biomarker in hepatocellular carcinoma.
Food for Thought: Addressing a Research Gap for Dietary Trials in Hematologic Malignancies.

bioRxiv. 2025 Aug 02. pii: 2025.08.01.668168. [Epub ahead of print]

Distinct proteomic and acylproteomic adaptations to succinate dehydrogenase loss in two cell contexts.

Sherry X Zhou, Benjamin Madden, Cristine Charlesworth, Taro Hitosugi, Judith Favier, Louis J Maher.

BACKGROUND: The tricarboxylic acid (TCA) cycle and electron transport chain (ETC) are key metabolic pathways required for cellular ATP production. While loss of components in these pathways typically impairs cell survival, such defects can paradoxically promote tumorigenesis in certain cell types. One such example is loss of succinate dehydrogenase (SDH), which functions in both the TCA cycle and as Complex II of the ETC. Deleterious mutations in SDH subunits can cause pheochromocytoma and paraganglioma (PPGL), rare hereditary neuroendocrine tumors of chromaffin cells in the adrenal gland and the nerve ganglia, respectively. Why tumor formation upon SDH loss is limited to certain tissues remains unclear. We hypothesized that the metabolic and proteomic perturbations resulting from SDH loss are cell-type specific, favoring survival of chromaffin cells.
METHODS: We comprehensively examined the proteomic, acetylproteomic, and succinylproteomic effects of SDH loss in two cell models, immortalized mouse chromaffin cells (imCCs) and immortalized mouse embryonic fibroblasts (iMEFs). Perturbations in metabolite levels were determined by mass spectrometry. Effects of SDH loss on fatty acid β-oxidation (FAO) were assessed by stable isotope tracing and pharmacologic inhibition.
RESULTS: SDH-loss imCCs show significant upregulation of mitochondrial proteins, including TCA cycle and FAO enzymes, with pronounced downregulation of nuclear proteins. Both imCCs and iMEFs demonstrate significant energy deficiency upon SDH loss, but FAO activity is uniquely increased in SDH-loss imCCs. While SDH loss increases both lysine-reactive acetyl-CoA and succinyl-CoA, SDH-loss imCCs and iMEFs show disproportionate hyperacetylation but mixed succinylation. Surprisingly, SDH-loss imCCs, but not iMEFs, display disproportionate hypoacetylation and hyposuccinylation of mitochondrial proteins.
CONCLUSIONS: SDH loss differentially impacts the proteomes and acylproteomes of imCCs and iMEFs, with compartment-specific effects. These findings reveal cell type-specific adaptations to SDH loss. The plasticity of the response of imCCs may underlie the tissue-specific susceptibility to tumorigenesis and could illuminate therapeutic vulnerabilities of SDH-loss tumors.

DOI: https://doi.org/10.1101/2025.08.01.668168
Cell Metab. 2025 Jul 30. pii: S1550-4131(25)00333-X. [Epub ahead of print]

Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control.

Joseph Longo, Lisa M DeCamp, Brandon M Oswald, Robert Teis, Alfredo Reyes-Oliveras, Michael S Dahabieh, Abigail E Ellis, Michael P Vincent, Hannah Damico, Kristin L Gallik, Nicole M Foy, Shelby E Compton, Colt D Capan, Kelsey S Williams, Corinne R Esquibel, Zachary B Madaj, Hyoungjoo Lee, Dominic G Roy, Connie M Krawczyk, Brian B Haab, Ryan D Sheldon, Russell G Jones.

  Glucose is essential for T cell proliferation and function, yet its specific metabolic roles in vivo remain poorly defined. Here, we identify glycosphingolipid (GSL) biosynthesis as a key pathway fueled by glucose that enables CD8+ T cell expansion and cytotoxic function in vivo. Using 13C-based stable isotope tracing, we demonstrate that CD8+ effector T cells use glucose to synthesize uridine diphosphate-glucose (UDP-Glc), a precursor for glycogen, glycan, and GSL biosynthesis. Inhibiting GSL production by targeting the enzymes UDP-Glc pyrophosphorylase 2 (UGP2), UDP-Gal-4-epimerase (GALE), or UDP-Glc ceramide glucosyltransferase (UGCG) impairs CD8+ T cell expansion upon pathogen challenge. Mechanistically, we show that glucose-dependent GSL biosynthesis is required for plasma membrane lipid raft integrity and optimal T cell receptor (TCR) signaling. Moreover, UGCG-deficient CD8+ T cells display reduced granzyme expression, cytolytic activity, and tumor control in vivo. Together, our data establish GSL biosynthesis as a critical metabolic fate of glucose-beyond energy production-that is required for CD8+ T cell responses in vivo.

Keywords:  CD8(+) T cells; UGCG; cytotoxic function; glucose; glycosphingolipids; immunometabolism; lipid rafts; lipidomics; metabolomics; nucleotide sugar metabolism

DOI:  https://doi.org/10.1016/j.cmet.2025.07.006
Curr Pharmacol Rep. 2024 Dec;10(6): 388-404

Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.

Patryk Firmanty, Monika Chomczyk, Shubhankar Dash, Marina Konopleva, Natalia Baran.

   Purpose of Review: Acute myeloid leukemia (AML) is a clonal blood neoplasm with dismal prognosis. Despite the introduction of many novel targeted agents, cytotoxic chemotherapy has remained the standard of care for AML. Differences in mitochondrial metabolism between normal and leukemic cells can be targeted by novel AML therapies, but these agents require a comprehensive efficacy and cytotoxicity evaluation.
Recent Findings: Metabolic alterations in AML blasts increase their sensitivity to therapies targeting mitochondrial metabolism. Targeting altered mitochondrial metabolism, that is crucial for leukemia cell growth and survival, could be a breakthrough in AML treatment. Therefore, BH3 family proteins, mitochondrial complexes, the tricarboxylic acid cycle, and amino acid (AA) and fatty acid metabolism are common treatment targets in AML. Although many drugs targeting these vulnerabilities showed acceptable safety profiles and promising efficacy in preclinical studies, clinical trials often do not confirm these results limited by narrow therapeutic window. The most effective regimens are based on drug combinations with synergistic or additive activity.
Summary: In this review, we present an overview of the most recent studies targeting mitochondrial metabolism in AML. We highlight that targeting of the specific energy metabolism dependencies of AML blasts provides an opportunity to achieve long-term responses with a reasonable safety profile. We emphasize that currently used drugs and their combinations display dose-limiting toxicities or are not efficient enough to completely eradicate leukemic stem cells. Thus, further studies of complex metabolic rewiring of leukemia cells before and after combinatorial therapies are warranted.

Keywords:  Acute myeloid leukemia; Metabolic reprogramming; Mitochondrial metabolism; Safety; Therapeutic interventions

DOI:  https://doi.org/10.1007/s40495-024-00378-8
J Ovarian Res. 2025 Aug 02. 18(1): 174

The effects of dietary fat on gut microbial composition and function in a mouse model of ovarian cancer.

Mariam M AlHilli, Naseer Sangwan, Alex Myers, Surabhi Tewari, Daniel J Lindner, Gail A M Cresci, Ofer Reizes.

OBJECTIVES: The gut microbiome (GM) is pivotal in regulating inflammation, immune responses, and cancer progression. This study investigates the effects of a ketogenic diet (KD) and a high-fat/low-carbohydrate (HF/LC) diet on GM alterations and tumor growth in a syngeneic mouse model of high-grade serous ovarian cancer (EOC).
METHODS: Thirty female C57BL/6 J mice injected with KPCA cells were randomized into KD, HF/LC, and low-fat/high-carbohydrate (LF/HC) diet groups. Tumor growth was monitored with live, in vivo imaging. Stool samples were collected at the time of euthanasia and analyzed by 16SrRNA sequencing and shotgun metagenomic sequencing was performed to identify differential microbial taxonomic composition and metabolic function.
RESULTS: Our findings revealed that KD and HF/LC diets significantly accelerated EOC tumor growth compared to the LF/HC diet in a xenograft model. GM diversity was markedly reduced in KD and HF/LC-fed mice, correlating with increased tumor growth, whereas LF/HC-fed mice showed higher GM diversity. Metagenomic analyses identified distinct alterations in microbial taxa including Bacteroides, Lachnospiracae bacterium, Bacterium_D16_50, and Enterococcus faecalis predominantly abundant in HF/LC-fed mice, Dubsiella_newyorkensis predominantly abundant in LF/HC-fed, and KD fed mice showing a higher abundance of Akkermansia and Bacteroides. Functional pathways across diet groups indicated polyamine biosynthesis and fatty acid oxidation pathways were enriched in HF/LC-fed mice.
CONCLUSIONS: These results highlight the intricate relationship between diet andthe gut microbiome in promoting EOC growth. The potential role of dietary interventions in cancer prevention and treatment warrants further investigation.

DOI: https://doi.org/10.1186/s13048-025-01731-1
Curr Opin Clin Nutr Metab Care. 2025 Aug 08.

Ketogenic diet in the management of disease.

Thien Luong, Mads Svart, Lars Christian Gormsen, Esben Søndergaard.

   PURPOSE OF REVIEW: The ketogenic diet has gained renewed attention as a nutritional intervention across a range of chronic diseases. This review evaluates the recent clinical evidence supporting ketogenic diet applications beyond epilepsy, with a focus on cardiometabolic, neurodegenerative, psychiatric, and oncological conditions.
RECENT FINDINGS: Ketogenic diet improves insulin sensitivity and glycemic control in obesity and type 2 diabetes, effect that are partly attributable to weight loss, but also include reduced postprandial glucose excursions, lower insulin levels, and altered substrate metabolism. In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, ketogenic diet may increase substrate availability, cerebral perfusion and cognition function. Preliminary data from uncontrolled studies suggests potential benefits in severe mental illness. In oncology, ketogenic diet may influence tumor metabolism via glucose restriction, but clinical efficacy as an adjunct therapy remains unproven. Across studies, conclusions are limited by short intervention durations, inconsistent protocols, low dietary adherence, and high interindividual variability in metabolic response.
SUMMARY: Although emerging data suggest therapeutic potential of ketogenic diet across several conditions, routine clinical implementation is premature. Future trials should employ standardized dietary protocols and assess long-term, clinically relevant outcomes to establish safety and efficacy.

Keywords:  cancer; cardiometabolic disease; ketogenic diet; neurodegenerative disease; psychiatric disease

DOI:  https://doi.org/10.1097/MCO.0000000000001158
bioRxiv. 2025 Aug 01. pii: 2025.07.29.667471. [Epub ahead of print]

Alanine Catabolism as a Targetable Vulnerability for MYC-Driven Liver Cancer.

Tonatiuh Montoya, Joyce V Lee, Longhui Qiu, Abigail Krall, Nedas Matulionis, Yurim Seo, Brian N Finck, Robin K Kelley, Heather Christofk, Andrei Goga.

Liver cancer is a leading cause of cancer-related death world-wide in part due to the shortage of effective therapies, and MYC overexpression defines an aggressive and especially difficult to treat subset of patients. Given MYC's ability to reprogram cancer cell metabolism, and the liver's role as a coordinator of systemic metabolism, we hypothesized that MYC induces metabolic dependencies that could be targeted to attenuate liver tumor growth. We discovered that MYC-driven liver cancers catabolize alanine in a GPT2-dependent manner to sustain their growth. GPT2 is the predominant alanine-catabolizing enzyme expressed in MYC-driven liver tumors and genetic ablation of GPT2 limited MYC-driven liver tumorigenesis. In vivo isotope tracing studies uncovered a role for alanine as a substrate for a repertoire of pathways including the tricarboxylic acid cycle, nucleotide production, and amino acid synthesis. Treating transgenic MYC-driven liver tumor mouse models with L-Cycloserine, a compound that inhibits GPT2, was sufficient to diminish the frequency of mouse tumor formation and attenuate growth of established human liver tumors. Thus, we identify a new targetable metabolic dependency that MYC-driven liver tumors usurp to ensure their survival.

DOI: https://doi.org/10.1101/2025.07.29.667471
Front Nutr. 2025 ;12 1535921

Impact of ketogenic diets on cancer patient outcomes: a systematic review and meta-analysis.

Meiying Zhang, Qing Zhang, Sheng Huang, Yifu Lu, Mengyun Peng.

   Background: The ketogenic diet, characterized by high fat, moderate protein, and extremely low carbohydrate intake, has been widely used as a medical treatment for various conditions and has gained increasing attention in recent years due to its health benefits.
Objectives: This study aims to investigate the effectiveness of a ketogenic diet on outcomes in cancer patients compared to conventional non-ketogenic diets.
Materials and methods: Studies that assigned cancer patients to either a ketogenic diet or a standard diet control group were included. Two reviewers independently extracted and analyzed the data.
Results: This meta-analysis revealed that the ketogenic diet significantly reduced fat mass, visceral fat, insulin levels, blood glucose, fatigue, and insomnia compared to a non-ketogenic diet while improving low-density lipoprotein (LDL) cholesterol, total cholesterol, thyroid-stimulating hormone (TSH) levels, protein uptake, ketosis events, emotional function, and social function. Furthermore, the ketogenic diet induced ketosis by increasing β-hydroxybutyrate levels.
Conclusion: The ketogenic diet was found to improve cancer patients' outcomes more effectively than non-ketogenic diets. Notably, C-reactive protein levels showed greater improvement when the intervention lasted more than 12 weeks, with a diet composition of 2-4% carbohydrates, 16-18% protein, and 80-85% fat.
Systematic review registration: (https://www.crd.york.ac.uk/PROSPERO/view/CRD42024553878) PROSPERO CRD4202455387.

Keywords:  diets; ketogenic; ketogenic diet; systematic review and meta-analysis; tumor

DOI:  https://doi.org/10.3389/fnut.2025.1535921
bioRxiv. 2025 Jul 24. pii: 2025.07.23.666448. [Epub ahead of print]

Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.

Milan R Savani, Bailey C Smith, Wen Gu, Yi Xiao, Gerard Baquer, Bingbing Li, Skyler S Oken, Namya Manoj, Lauren G Zacharias, Vinesh T Puliyappadamba, Sylwia A Stopka, Michael S Regan, Michael M Levitt, Charles K Edgar, William H Hicks, Soummitra Anand, Tracey Shipman, Misty S Martin-Sandoval, Rainah Winston, João S Patrício, Xandria Johnson, Trevor S Tippetts, Diana D Shi, Andrew Lemoff, Timothy E Richardson, Pascal O Zinn, Ashley Solmonson, Thomas P Mathews, Nathalie Y R Agar, Ralph J DeBerardinis, Kalil G Abdullah, Samuel K McBrayer.

Conventional stable isotope tracing assays track one or several metabolites. However, cells use an array of nutrients to sustain nitrogen metabolic pathways. This incongruency hampers a system level understanding of cellular nitrogen metabolism. Therefore, we created a platform to simultaneously trace 30 nitrogen isotope-labeled metabolites. This platform revealed that while primitive cells engage both de novo and salvage pyrimidine synthesis pathways, differentiated cells nearly exclusively salvage uridine despite expressing de novo pathway enzymes. This link between cell state and pyrimidine synthesis routes persisted in physiological contexts, including primary murine and human tissues and tumor xenografts. Mechanistically, we found that Ser1900 phosphorylation of CAD, the first enzyme of the de novo pathway, was enriched in primitive cells and that mimicking this modification in differentiated cells abrogated their preference for pyrimidine salvage. Collectively, we establish a method for nitrogen metabolism profiling and define a mechanism of cell state-specific pyrimidine synthesis pathway choice.

DOI: https://doi.org/10.1101/2025.07.23.666448
J Biol Chem. 2025 Jul 31. pii: S0021-9258(25)02406-8. [Epub ahead of print] 110555

Cysteine Oxidation of a Redox Hub within Complex I can Facilitate Electron Transport Chain Supercomplex Formation.

Runtai Chen, Seyed Amirhossein Tabatabaei Dakhili, Rokas Geruskis, Yuan Yuan Zhao, Steven Lockhart, Lusine Tonoyan, Arno Siraki, Guocheng Huang, Adam Kinnaird, Darren H Freed, Shelley Minteer, Evangelos D Michelakis, John R Ussher, Gopinath Sutendra.

  The mitochondrial Electron Transport Chain (ETC) is a four complex unit that could be considered the most essential infrastructure within the mitochondria, as it primarily functions to generate the mitochondrial membrane potential (ΔΨm, the cells equivalent to battery capacity), which can then be utilized for ATP synthesis or heat production. Another important aspect of ETC function is the generation of mitochondrial reactive oxygen species (mtROS), which are essential physiologic signaling mediators that can be toxic to the cell if their levels become too high. Currently, it remains unresolved how a highly utilized and functioning ETC can sense excessive mtROS generation and adapt, to enhance ΔΨm. Here we identified a redox hub consisting of cysteine (Cys) residues 64, 75, 78 and 92 within Ndufs1 of complex I of the ETC. Oxidation of these Cys residues promotes the incorporation of complex I into the respirasome supercomplex. Mechanistically, oxidation of the redox hub increased the distance between Fe-S clusters N5 and N6a in complex I, compromising complex I activity. This impairment was rescued by integration with complex III2 and IV into the respirasome supercomplex. Compared to parental cells or Ndufs1-KO cells, C92D (an oxidation mimetic) Ndufs1-knockin A549 cells had higher levels of ETC supercomplexes, ΔΨm and oxygen consumption rates, while isolated mitochondrial membranes generated more electrical current when integrated onto a biobattery platform. Knockdown of complex III2 significantly reduced complex I activity (within the respirasome) from C92D Ndufs1-knockin cells, but not parental A549 cells. Finally, disruption of ETC supercomplexes with the small molecule drug MitoTam increased the therapeutic efficacy of mtROS inducing chemotherapeutics in both C92D Ndufs1-knockin or metastatic lung cancer cells. These findings provide new insights into how the ETC can initiate supercomplex transformation.

Keywords:  Cancer Resistance; Cysteine Oxidation; Electron Transport Chain; Mitochondria; Reactive Oxygen Species; Supercomplex

DOI:  https://doi.org/10.1016/j.jbc.2025.110555
Cell Metab. 2025 Aug 05. pii: S1550-4131(25)00331-6. [Epub ahead of print]37(8): 1619-1620

Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice.

Takuya Karasawa, Ran Hee Choi, Cesar A Meza, Subhasmita Rout, Micah J Drummond, Amandine Chaix, Katsuhiko Funai.

Loss of lean mass is a potential concern for semaglutide-induced weight loss. This study indicates that semaglutide has unexpected effects on skeletal muscle mass and strength in mice, demonstrating a need to more carefully assess these effects in humans.

DOI: https://doi.org/10.1016/j.cmet.2025.07.004
Blood Neoplasia. 2025 Aug;2(3): 100121

PPARγ-induced upregulation of fatty acid metabolism confers resistance to venetoclax and decitabine therapy in AML.

Kotoko Yamatani, Tatsuro Watanabe, Kaori Saito, Abdullah Khasawneh, Abhishek Maiti, Zhihong Zeng, Kala Hayes, Shinya Kimura, Courtney D DiNardo, Xiaoping Su, Shuko Nojiri, Yasushi Okazaki, Michael Andreeff, Marina Konopleva, Yoko Tabe.

The combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC; VEN/DEC) constitutes a primary therapeutic strategy for treating older adults with acute myeloid leukemia (AML). However, a notable subset of patients exhibits resistance to VEN/DEC, demonstrating either no disease response or relapse after initial remission. This study aimed to elucidate the molecular mechanisms underlying this resistance through analyses of gene expression and DNA methylation profiles. We conducted comprehensive RNA sequencing analysis and DNA methylation profiling on AML samples from 35 patients undergoing VEN/DEC therapy. The RNA sequencing analysis revealed that several genes related to fatty acid metabolism were significantly upregulated in leukemia cells from patients who received VEN/DEC treatment and relapsed or failed to respond. Increased expression of peroxisome proliferator-activated receptor gamma (PPARG) occurred after treatment and correlated with decitabine-induced promoter hypomethylation. Subsequent in vitro validation demonstrated that decitabine treatment results in hypomethylation of the PPARG promoter, elevating PPARG levels and promoting a metabolic environment characterized by enhanced fatty acid oxidation pathways conducive to VEN/DEC resistance. Furthermore, pharmacological inhibition using either a PPARγ antagonist or a fatty acid oxidation inhibitor enhanced the sensitivity of resistant cells to VEN/DEC, underscoring the crucial role of PPARγ in the development of therapeutic resistance. These findings not only shed light on the metabolic adaptation that contributes to VEN/DEC resistance in AML but also identify PPARγ as a potential therapeutic target for overcoming such resistance, providing new opportunities to improve the efficacy of VEN/DEC-based therapy in AML.

DOI: https://doi.org/10.1016/j.bneo.2025.100121
Biomed Pharmacother. 2025 Aug 01. pii: S0753-3322(25)00620-1. [Epub ahead of print]190 118426

Donor-specific response of visceral adipocytes differentiated from human adipose-derived mesenchymal stem cells to branched-chain alpha-keto acid (BCKA) dehydrogenase activation.

Elżbieta Supruniuk, Agnieszka Mikłosz, Bartłomiej Łukaszuk, Marcin Baranowski, Adam Paszko, Łukasz Szczerbiński, Kamil Grubczak, Aleksandra Starosz, Adrian Chabowski.

   AIMS: The causal role of branched-chain amino acids (BCAAs) and their transamination derivatives (branched-chain α-ketoacids, BCKAs) was observed in the progression of obesity and its metabolic complications. In the study, we aimed to stimulate BCAA catabolic flux with an inhibitor of BCKA dehydrogenase kinase (i.e., BT2) to explore metabolic consequences using visceral ADMSCs, obtained from non-obese men and men with obesity, and differentiated to adipocytes.
MATERIALS AND METHODS: ADMSCs metabolism was assessed using real-time PCR, Western Blot, Ultra-High Performance Liquid Chromatography, Gas-Liquid Chromatography, Seahorse analysis, liquid scintillation counting, flow cytometry, immunofluorescence and spectrophotometric assays.
RESULTS: We report that obesity was associated with the redistribution of fatty acid transporters among a higher number of adipocytes (higher number of CD36/SR-B2 and FATP4 positive cells), but at the same time lowered surface abundance of transporters per cell (CD36/SR-B2, FATP1, FATP4, FABPpm). Despite that, the metabolic consequences of BT2 administration were strictly associated with the donor-specific inherent cellular properties, what enabled a differentiation of two adipocyte subpopulations with low and high metabolic activity. BT2 effects were more profound in the latter group, wherein pro-lipolytic and β-oxidation-related markers were upregulated, including higher ATP production, glycerol release and acid-soluble metabolites accumulation, reduced fatty acid synthase expression, decreased free fatty acids and triacylglycerols concentrations.
CONCLUSIONS: Our data highlight the substantial contribution of BCAA catabolism in adipocyte lipogenesis, and effective utilization of energy substrates. The more efficient the regulation of fat storage in the adipocytes, the less would be the lipotoxic effects in non-adipose tissues.

Keywords:  Cellular research; Drug mechanism; Experimental pharmacology; Weight management

DOI:  https://doi.org/10.1016/j.biopha.2025.118426
Sci Rep. 2025 Aug 05. 15(1): 28576

Role of metabolomic changes in diagnosis and assessment of treatment response in acute myeloid leukemia.

Shabbir Hussain, Farhat Bano, Muhammad Ikram Ullah, Rahat Abdul Rehman, Kausar Bano, Muhammad Asif Naveed.

  Acute Myeloid Leukemia (AML) is an aggressive cancer characterized by the rapid proliferation of abnormal myeloid cells. Despite advancements in treatment, patient outcomes remain variable, underscoring the need for more accurate diagnostic and prognostic tools. Metabolomics has gained attention for its potential to offer new insights into disease mechanisms and progression. This study aimed to compare metabolomic profiles between AML patients and normal controls, determine the diagnostic accuracy of different metabolites in AML patients, assess the diagnostic accuracy of specific metabolites in AML patients, and evaluate the prognostic significance of these metabolites at the first bone marrow follow-up. The cross-sectional study included 56 AML patients (sampled before and after chemotherapy) and 56 age- and sex-matched healthy controls. Whole blood and serum samples were collected from all participants after obtaining informed consent. Metabolomic analysis was performed using a Bruker 600 MHz NMR spectrometer. Results revealed significant metabolic alterations between AML patients and healthy controls, as well as in remission and non-remission groups. Key disrupted pathways included lipid metabolism, amino acid metabolism, and glycolysis (p < 0.05). Metabolite panels such as acetate, creatine, and lactate demonstrated strong diagnostic potential (AUC = 0.98), while citrate, glutamate, and choline panels (AUC = 0.89) showed prognostic utility in distinguishing patients from controls and remission from non-remission groups, respectively (p < 0.05). The study highlights significant metabolomic alterations in AML patients, marked by disruptions in lipid, energy, and amino acid metabolism, elevated glucose levels, and enhanced diagnostic and prognostic capabilities. These findings support the development of personalized diagnostic and therapeutic strategies.

Keywords:  Acute myeloid leukemia; Diagnostic biomarkers; Metabolomics; NMR; Prognostic biomarkers

DOI:  https://doi.org/10.1038/s41598-025-99845-5
bioRxiv. 2025 Jul 31. pii: 2025.07.28.667273. [Epub ahead of print]

Assessing cellular metabolic dynamics with NAD(P)H fluorescence polarization imaging.

Lu Ling, Jack C Crowley, Matthew L Tan, Jennie A M R Kunitake, Adrian A Shimpi, Rebecca M Williams, Lara A Estroff, Claudia Fischbach, Warren R Zipfel.

Altered metabolism enables adaptive advantages for cancer, driving the need for improved methods for non-invasive long-term monitoring of cellular metabolism from organelle to population level. Here we present two-photon steady-state fluorescence polarization ratiometric microscopy (FPRM), a label-free imaging method that uses nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) autofluorescence as a functional readout of cellular metabolism. The method is simple to implement and operates an order of magnitude faster than the NAD(P)H-fluorescence lifetime imaging microscopy (FLIM) imaging modality, reducing cytotoxic stress while providing long-term monitoring capacity. FPRM enables high-resolution dynamic tracking of NAD(P)H signals with subcellular details and we have established a set of instrument-independent ratiometric parameters that correlates NAD(P)H signals with metabolic status during pharmaceutical and environmental perturbations. We further integrated FPRM readouts with other parameters such as cell shape and migration on 2D and 3D collagen matrices, demonstrating the technique's versatility across bioengineered platforms for cancer metabolism research.

DOI: https://doi.org/10.1101/2025.07.28.667273
Nat Commun. 2025 Aug 08. 16(1): 7318

ATP allosterically regulates an acyl-CoA oxidase.

David H Perez, Arup Mondal, Weijie Xu, Valentina Baredes, Hannah E Connell, Alberto Perez, Rebecca A Butcher.

ATP is an important allosteric regulator of many enzymes, but these enzymes typically utilize ATP or other nucleotides as substrates. Acyl-CoA oxidase (ACOX) enzymes are central players in peroxisomal fatty acid metabolism, as well as in secondary metabolism in nematodes and plants. These dimeric enzymes have been shown to bind to ATP at unusual sites that are buried at the dimer interface. Here, we show that ATP stimulates the activity of an ACOX enzyme by increasing the binding affinity of the enzyme for its FAD cofactor. The effect of ATP is highly specific as other nucleotides do not stimulate the activity of the enzyme and mutation of the ATP binding site blocks the effect. We use X-ray crystallography and molecular dynamics simulations of the apo dimeric enzyme to identify an unprecedented mechanism whereby ATP can reach its binding site through a shift in an α-helix bundle. An allosteric network connects the ATP and FAD binding sites, enabling ATP to enhance FAD binding affinity and thus enzymatic activity. In summary, the binding of ACOX enzymes to FAD is allosterically controlled by ATP, potentially providing a link between ATP levels and primary and secondary metabolism.

DOI: https://doi.org/10.1038/s41467-025-61905-9
STAR Protoc. 2025 Aug 02. pii: S2666-1667(25)00410-1. [Epub ahead of print]6(3): 104004

Protocol for measuring mitochondrial respiratory capacity from buccal cell swabs.

Tina R Ram, Chunlong Mu, Jaclyn C Campbell, Sarah J MacEachern, Jane Shearer.

  Mitochondrial respirometry provides a detailed assessment of oxygen consumption within the electron transport system, yet methods detailing respiration from non-invasive samples remain limited. Here, we present a protocol for measuring mitochondrial respiration in cultured buccal cells. We outline procedures for buccal cell collection, primary cell culture, and respirometry calibration, followed by oxygen consumption measurements and cell count for data normalization. This protocol allows reliable evaluation of mitochondrial function from non-invasive buccal cell samples, offering a valuable tool for metabolic investigation.

Keywords:  Cell Biology; Cell culture; Cell-based Assays; Metabolism

DOI:  https://doi.org/10.1016/j.xpro.2025.104004
bioRxiv. 2025 Aug 01. pii: 2025.08.01.668058. [Epub ahead of print]

Differential Bioenergetic Profile of Human Glioblastoma following Transplantation of Myocyte-derived Mitochondria.

Kent L Marshall, Ethan Meadows, Alan Mizener, John M Hollander, Christopher P Cifarelli.

Glioblastoma (GBM) exhibits profound plasticity, enabling adaptation to fluctuating microenvironmental stressors such as hypoxia and nutrient deprivation. However, this metabolic rewiring also creates subtype-specific vulnerabilities that may be exploited therapeutically. Here, we investigate whether mitochondrial transplantation using non-neoplastic, human myocyte-derived mitochondria alters the metabolic architecture of GBM cells and modulates their response to ionizing radiation. Using a cell-penetrating peptide-mediated delivery system, we successfully introduced mitochondria into two mesenchymal-subtype GBM cell lines, U3035 and U3046. Transplanted cells exhibited enhanced mitochondrial polarization and respiratory function, particularly in the metabolically flexible U3035 line. Bioenergetic profiling revealed significant increases in basal respiration, spare respiratory capacity, and glycolytic reserve in U3035 cells post-transplantation, whereas U3046 cells showed minimal bioenergetic augmentation. Transcriptomic analyses using oxidative phosphorylation (OXPHOS) and glycolysis gene sets confirmed these functional findings. At baseline, U3035 cells expressed high levels of both glycolytic and OXPHOS genes, while U3046 cells were metabolically suppressed. Following radiation, U3035 cells downregulated key OXPHOS and glycolysis genes, suggesting metabolic collapse. In contrast, U3046 cells transcriptionally upregulated both pathways, indicating compensatory adaptation. These results identify and establish mitochondrial transplantation as a metabolic priming strategy that sensitizes adaptable GBM subtypes like U3035 to therapeutic stress by inducing bioenergetic overextension. Conversely, rigid subtypes like U3046 may require inhibition of post-radiation metabolic compensation for effective targeting. Our findings support a novel stratified approach to GBM treatment which integrates metabolic subtype profiling with bioenergetic modulation.

DOI: https://doi.org/10.1101/2025.08.01.668058
Trans Am Clin Climatol Assoc. 2025 ;135 196-205

OPPORTUNITIES AND CHALLENGES FOR TARGETING CANCER METABOLISM.

Chi V Dang.

Otto Warburg sparked the field of cancer metabolism in the 1920s through his observations that human and animal cancer tissues converted significant amounts of glucose to lactate with an elusive underlying mechanism. The discovery of oncogenes led to the notion that neoplasia results from deregulated cell division control with metabolism at the margin, standing by to support cell growth. Studies over the past several decades have linked oncogenes to the direct regulation of metabolism, such as the myelocytomatosis (MYC) oncogene, driving glycolysis and other central metabolic pathways, necessary for cell growth and proliferation. Deregulated oncogenic drive of metabolism renders tumor cells addicted to glucose and other nutrients, such that nutrient deprivation can trigger cancer cell death. The revelation of this addiction stimulated pharmaceutical companies to target metabolism for cancer therapy, but due to several failed clinical studies, this exuberance fizzled commercially. However, the transformative impact of cancer immunotherapy ushered in an interest in understanding the hostile metabolic tumor microenvironment that limits the function of anti-tumor T cells and clinical responses to immunotherapy. This interest drives the convergence of immunometabolism and cancer cell metabolism research to provide a richer understanding of tumor metabolic vulnerability. Herein, I discuss the historical and current context of opportunities and challenges to targeting cancer metabolism.
Redox Biol. 2025 Aug 05. pii: S2213-2317(25)00321-0. [Epub ahead of print]86 103808

Age-related declines in mitochondrial Prdx6 contribute to dysregulated muscle bioenergetics.

Jose Adan Arevalo, Dianna Xing, Roberto Garcia Leija, Max A Thorwald, Diana Daniela Moreno-Santillán, Kaitlin N Allen, Giovanna Selleghin-Veiga, Heidi C Avalos, Eva Utke, Justin L Conner, George A Brooks, José Pablo Vázquez-Medina.

An age-related decline in mitochondrial function is a multi-factorial hallmark of aging, driven partly by increased lipid hydroperoxide levels that impair mitochondrial respiration in skeletal muscle, leading to atrophy. Although pharmacological and genetic manipulations to counteract increased lipid hydroperoxide levels represent a promising strategy to treat sarcopenia, the mechanisms driving such phenotypes remain understudied. Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme that contributes to peroxidized membrane repair via its phospholipid hydroperoxidase and phospholipase A2 activities. Here, we show decreased mitochondrial Prdx6 levels, increased mitochondrial lipid peroxidation, and dysregulated muscle bioenergetics in aged mice and muscle cells derived from older humans. Mechanistically, we found that Prdx6 supports optimal mitochondrial function and prevents mitochondrial fragmentation by limiting mitochondrial lipid peroxidation via its membrane remodeling activities. Our results suggest that age-related declines in mitochondrial Prdx6 contribute to dysregulated muscle bioenergetics, thereby opening the door to therapeutic modulation of Prdx6 to counteract diminished mitochondrial function in aging.

DOI: https://doi.org/10.1016/j.redox.2025.103808
medRxiv. 2025 Jul 21. pii: 2025.07.19.25331848. [Epub ahead of print]

Clinical and translational study of ivosidenib plus nivolumab in advanced solid tumors harboring IDH1 mutations.

Matthew K Nguyen, Mark Jelinek, Arjun Singh, Brian Isett, Erica S Myers, Steven J Mullett, Yvonne Eisele, Jan Beumer, Robert Parise, Julie Urban, Amy Rose, Lorenzo Sellitto, Krishna Singh, Rose Doerfler, Rebekah E Dadey, Carl Kim, John C Rhee, Diwakar Davar, Liza C Villaruz, Melissa Burgess, Jan Drappatz, Megan Mantica, Amy E Goodman, Hong Wang, Aatur D Singhi, Jason J Luke, Dan P Zandberg, Riyue Bao.

Background: Cancers that do not respond to immunotherapy typically harbor a non-T cell-inflamed tumor microenvironment (TME), characterized by the absence of type I/II interferon (IFN) signaling and CD8 + T cell infiltration. We previously reported IDH1 somatic mutations were enriched in non-T cell-inflamed tumors across tumor types. Consistent with this, mutant IDH1 (mIDH1) has been demonstrated to drive immune exclusion through metabolic reprogramming of the TME, and IDH inhibition enhanced anti-tumor immunity in preclinical models. Based on these pan-cancer observations, we conducted a Phase II study assessing the preliminary activity of ivosidenib, an IDH1 inhibitor, in combination with nivolumab, an anti-PD1 antibody, in patients with mIDH1 advanced solid tumors ( NCT04056910 ).
Methods: Patients with an advanced or refractory solid tumor harboring an IDH1 mutation, but no prior exposure to IDH1 inhibitor, were enrolled. Participants were administered ivosidenib 500 mg by mouth daily with nivolumab 480 mg intravenously every 4 weeks. Given heterogeneity in tumor types, including some where RECIST response is uncommon (i.e. sarcoma), a composite primary endpoint was utilized including either six-month progression free survival (PFS6) or overall response rate (ORR). Translational analyses included pharmacodynamic, proteomic, and spatial transcriptomic investigations.
Results: 15 patients were enrolled (median age, 54 years; female, 53.3%; ECOG 1, 60%; glioma, 46.7%; R132H, 40%). One patient had a partial response (ORR 6.7%) and was without progression at 6 months (PFS6) whereas two other patients achieved PFS6 alone. In total, 3 out of 15 patients met the primary endpoint (3/15; 20%). The median PFS was 1.94 months. The most common treatment adverse events were leukopenia (67%), rash (67%), diarrhea (33%), nausea (27%), and QTC prolongation (27%). Pharmacodynamic studies demonstrated combining ivosidenib and nivolumab significantly decreased the plasma (R)-2HG concentration and correlated with clinical benefit. Serum proteomic and spatial omic analysis suggested immune-modulatory effects of mIDH1 inhibition plus anti-PD1.
Conclusions: In treatment refractory mIDH1 solid tumors, the combination of ivosidenib and nivolumab was safe however demonstrated similar anti-tumor activity (predominantly as disease stabilization) compared with that previously described for ivosidenib monotherapy. Translational investigation suggests further evaluation of IDH1 inhibition as a combination partner with immune-checkpoint inhibition may be justified.
Implications for practice: This study demonstrates that ivosidenib combined with nivolumab was safe in patients with advanced IDH1-mutant solid tumors. The clinical activity was modest and comparable to ivosidenib monotherapy. Pharmacodynamic and exploratory translational analyses revealed immune-related changes in the tumor microenvironment, suggesting that mutant IDH1 inhibition may modulate immune signaling. These findings support further investigation of IDH1 inhibitors as immunotherapy partners and highlight the importance of integrated translational analyses to inform therapeutic development.

DOI: https://doi.org/10.1101/2025.07.19.25331848
Front Cell Dev Biol. 2025 ;13 1642006

Inhibiting the RNA helicase DDX3X in Burkitt lymphoma induces oxydative stress and impedes tumor progression in xenografts.

Hugues Beauchemin, Zeinab Dalloul, Eva-Maria Piskor, Virginie Calderon, Andrew Chatr-Aryamontri, Thierry Bertomeu, Tarik Möröy.

   Introduction: Burkitt Lymphoma (BL), an aggressive B-cell lymphoma driven by MYC translocations, requires intensive chemotherapy treatments which deliver high effectiveness yet increase future risks of developing secondary malignancies. We have previously shown that DDX3X, an RNA helicase frequently mutated in BL, is essential for B cell lymphomagenesis in mice.
Methods and results: To assess if DDX3X could therefore represent a promising therapeutic target for BL, we tested two DDX3X inhibitors, the well characterized RK-33 and the more potent newly developed C1, in three BL cell lines (CA46, Raji, Daudi). We found that the 3 cell lines exhibited differential sensitivities to the drugs in vitro, with Daudi being the most susceptible and Raji the most resistant. In vivo, RK-33 treatment in a xenograft BL model reduced tumor progression in all cell lines, albeit with variable efficacy compared to the clinical drug Pevonedistat, and again with the Daudi cells being the most responsive to the treatment. Transcriptomic and proteomic analyses indicated that RK-33-mediated inhibition of DDX3X, and DDX3X ablation through siRNA affects oxidative phosphorylation among other pathways and leads to an increase of intracellular reactive oxygen species (ROS). A CRISPR chemogenomic screen to identify synthetic lethalities linked to RK-33 implicated enzymes of the glutathione synthesis pathway and the Keap1-Nrf2-ARE pathway. We therefore tested the inhibition of the glutathione pathway with buthionine sulfoximine and showed that it reduced the CC50 of RK-33 in BL cells lines.
Conclusion: Our findings not only support DDX3X as a therapeutic target in BL but also provide evidence for a combinatorial treatment strategy to improve the efficacy of current treatments.

Keywords:  ATP-dependent RNA helicase; Burkitt lymphoma (BL); DDX3 as a potential target; DDX3 inhibitor; RNA helicase; xenograft

DOI:  https://doi.org/10.3389/fcell.2025.1642006
J Physiol Biochem. 2025 Aug 05.

Alpha-ketoglutarate supplementation differently modifies hematological parameters and oxidative stress in mice fed a standard diet and high-fat high-fructose diet.

Myroslava V Vatashchuk, Viktoriia V Hurza, Oleksandra B Abrat, Maria P Lylyk, Khrystyna Matvieieva, Dmytro V Gospodaryov, Oleh I Demianchuk, Kenneth B Storey, Maria M Bayliak, Volodymyr I Lushchak.

  Long-term consumption of high-calorie diets can lead to metabolic disorders. In this study, we evaluated the effects of an eight-week standard (control), high-fat high-fructose (HFFD), alpha-ketoglutarate (AKG)-supplemented (1% in drinking water), and combined diet (HFFD + AKG) on hematological and oxidative stress parameters across tissues of male C57BL/6J mice. Both HFFD and AKG decreased erythrocyte count and altered leukocyte profile, increasing neutrophils and monocytes while decreasing lymphocytes. HFFD increased visceral fat mass and intensified oxidative stress in adipose tissue, as indicated by elevated lipid peroxide (LOOH) levels. LOOH levels in adipose tissue of AKG- and HFFD + AKG-fed mice matched control. HFFD or AKG lowered glutathione peroxidase and NAD(P)H-quinone oxidoreductase 1 (NQO1) activities in adipose tissue relative to control, unlike HFFD + AKG-fed counterparts. The heart showed an adaptive response to HFFD, with increased glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase, and NQO1 activities, and lower levels of oxidized glutathione (GSSG). AKG increased reduced glutathione (GSH) levels and elevated GPx and GST activities in the heart, whereas HFFD + AKG-fed mice had lower LOOH levels than HFFD-fed counterparts. Similarly, HFFD and AKG decreased GSSG and increased GSH in skeletal muscle. Both AKG- and HFFD + AKG-fed mice had lower carbonyl protein levels in muscle compared to control and HFFD-fed mice. Like adipose, muscle of HFFD- and AKG-fed mice had lower NQO1 activity compared to control, unlike HFFD + AKG group. These findings suggest AKG may mitigate HFFD-induced oxidative stress and modulate hematological parameters, with tissue- and diet-dependent effects, suggesting its role as an antioxidant under metabolic stress and a regulator of baseline redox homeostasis.

Keywords:  Alpha-ketoglutarate; Functional food; High-calorie diet; Mice; Nutrition; Oxidative stress

DOI:  https://doi.org/10.1007/s13105-025-01115-5
Ther Adv Hematol. 2025 ;16 20406207251343116

Safety of venetoclax in real-world experience: data from the French national database of pharmacovigilance through all indications in hematological malignancies over 5 years.

Alexis Talbot, Pierre-Edouard Debureaux, Agnès Lillo-Le Louet, Yasmine Derri, Marine Aroux-Pavard, Hélène Jantzem, David M Smadja, Cyrille Touzeau, Christine Le Beller, Nicolas Gendron.

   Background: Venetoclax is the first representative of a new class of targeted therapy, that inhibits selectively B-cell lymphoma-2 (BCL-2), an anti-apoptotic protein, frequently overexpressed in hematological malignancies. Venetoclax was approved by the Food and Drug Administration for chronic lymphocytic leukemia and for acute myeloid leukemia in 2016 and 2021, respectively. Because of its promising role in many hematological malignancies, several clinical trials are in progress and other extensions of indication are expected. An analysis of its long-term safety profile in real life is necessary.
Objectives: The aim of our study was to evaluate all adverse events (AEs) reported to the French national pharmacovigilance database since its approval in France.
Methods: We performed a retrospective study of all cases of AEs occurring under venetoclax recorded in the French national pharmacovigilance database since its market approval until March 2022 in France.
Results: During the period study, a total of 209 AEs were spontaneously reported in 123 patients, of which 173 (82%) were serious. We confirmed that the most frequent toxicities described by the summary of product characteristic (SPC) and literature data on it, including hematological (21%), gastrointestinal (11%), dermatological (9%), infectious (8%) AEs, and tumor lysis syndrome (3%). Seventy-six (36%) AEs were not listed in the SPC for which the causal relationship of venetoclax could not be excluded including autoimmune hemolytic anemias (2%) or cardiac AEs (7%).
Conclusion: These data especially in cardiac events provide important information on the safety of the venetoclax in a real-world setting.

Keywords:  acute myeloid leukemia; chronic lymphocytic leukemia; pharmacovigilance; real-world; safety; venetoclax

DOI:  https://doi.org/10.1177/20406207251343116
Redox Biol. 2025 Aug 05. pii: S2213-2317(25)00326-X. [Epub ahead of print]86 103813

Asparagine synthetase modulates glutaminase inhibitor sensitivity through metabolic reprogramming and serves as a prognostic biomarker in hepatocellular carcinoma.

Benjian Gao, Dongning Zheng, Hong Liu, Yu Guo, Yuntao Ye, Zhou Chen, Fengyi Yang, Jie Liu, Guangnian Zhang, Guoying Feng, Yongfa Liu, Qiang Wang, Song Su, Xiaoli Yang, Bo Li.

  Glutamine addiction represents a metabolic vulnerability in hepatocellular carcinoma (HCC), making glutaminase inhibitor CB-839 therapy a promising approach. However, effective therapeutic strategies are not yet available. In this study, we aim to investigate the potential role of asparagine synthetase (ASNS) as a target for HCC therapy during CB-839 treatment. CB-839 suppressed HCC cell growth, triggered apoptosis, and induced oxidative stress along with the disruption of amino acid metabolism. Moreover, ASNS was induced by CB-839 treatment through the activation of the amino acid response pathway. ASNS was significantly upregulated in HCC tumor tissues and was positively associated with poor prognosis; indeed our results revealed that its overexpression facilitated the proliferation, migration, and invasion of HCC cells. Furthermore, ASNS increased glutaminolysis and glutathione synthesis through reprogramming glutamine metabolism to maintain intracellular redox homeostasis, thereby activating the mTOR pathway that contributed to HCC progression. ASNS knockdown sensitized HCC cells to CB-839 both in vitro and in vivo. Overall, ASNS modulated the sensitivity to CB-839 in HCC through metabolic reprogramming, potentially serving as a biomarker for CB-839 response and a promising therapeutic target for HCC.

Keywords:  Asparagine synthetase; CB-839; Glutamine metabolism; Hepatocellular carcinoma; Metabolic reprogramming

DOI:  https://doi.org/10.1016/j.redox.2025.103813
Blood Cancer Discov. 2025 Aug 08. OF1-OF6

Food for Thought: Addressing a Research Gap for Dietary Trials in Hematologic Malignancies.

Akash Patel, Shireen Kassam, Urvi A Shah.

There is growing interest from both patients and clinicians in understanding the role nutrition plays across hematologic malignancies. In this study, we highlight key unanswered questions related to studying dietary interventions in hematologic malignancies, including questions about how to conduct research, trial design considerations, and integrating dietary interventions into hematologic cancer care and policy.

DOI: https://doi.org/10.1158/2643-3230.BCD-25-0141