bims-mibica Biomed News
on Mitochondrial bioenergetics in cancer
Issue of 2025–09–14
fourteen papers selected by
Kelsey Fisher-Wellman, Wake Forest University
  1. An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells.
  2. Activator of apoptosis harakiri (HRK) localisation at mitochondria alters mitochondrial morphology independently of other BCL-2 proteins.
  3. Mending a mother's mitochondrial DNA.
  4. Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism.
  5. Defined media reveals the essential role of lipid scavenging in supporting cancer cell proliferation.
  6. NDUFS8 facilitates hepatocellular carcinoma growth by enhancing mitochondrial function and escaping HUWE1-dependent degradation.
  7. Mechanism of Na+ ions contribution to the generation and maintenance of a high inner membrane potential in mitochondria.
  8. Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells.
  9. PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias.
  10. Impact of Acute Myeloid Leukemia Cells on the Metabolic Function of Bone Marrow Mesenchymal Stem Cells.
  11. The Combination of Ibrutinib with BH3 Mimetics or Dichloroacetate Is Effective in B-CLL.
  12. Menin inhibition for the treatment of acute leukemia.
  13. The dual role of VDAC in cancer: Molecular mechanisms and advances in targeted therapy.
  14. Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival.
  1. Nat Metab. 2025 Sep 08.
    An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells.
    Faith C Kaluba, Thomas J Rogers, Yu-Jin Jeong, Rachel 'Rae' J House, Althea Waldhart, Kelly H Sokol, Samuel R Daniels, Cameron J Lee, Joseph Longo, Amy Johnson, Vincent J Sartori, Ryan D Sheldon, Russell G Jones, Evan C Lien.
      Cancer cells are exposed to diverse metabolites in the tumour microenvironment that are used to support the synthesis of nucleotides, amino acids and lipids needed for rapid cell proliferation. In some tumours, ketone bodies such as β-hydroxybutyrate (β-OHB), which are elevated in circulation under fasting conditions or low glycemic diets, can serve as an alternative fuel that is metabolized in the mitochondria to provide acetyl-CoA for the tricarboxylic acid (TCA) cycle. Here we identify a non-canonical route for β-OHB metabolism that bypasses the TCA cycle to generate cytosolic acetyl-CoA. We show that in cancer cells that can metabolize ketones, β-OHB-derived acetoacetate in the mitochondria can be shunted into the cytosol, where acetoacetyl-CoA synthetase (AACS) and thiolase convert it into cytosolic acetyl-CoA. This alternative metabolic routing allows β-OHB to avoid oxidation in the mitochondria and to be used as a major source of cytosolic acetyl-CoA, even when other key cytosolic acetyl-CoA precursors such as glucose are available in excess. Finally, we demonstrate that ketone body metabolism, including this alternative AACS-dependent route, can support the growth of mouse KrasG12D; Trp53-/- pancreatic tumours grown orthotopically in the pancreas of male mice, as well as the growth of mouse B16 melanoma tumours in male mice fed a calorie-restricted diet. Together, these data reveal how cancer cells use β-OHB as a major source of cytosolic acetyl-CoA to support cell proliferation and tumour growth.
    DOI:  https://doi.org/10.1038/s42255-025-01366-y
  2. FEBS J. 2025 Sep 12.
    Activator of apoptosis harakiri (HRK) localisation at mitochondria alters mitochondrial morphology independently of other BCL-2 proteins.
    Louise E King, Lukas Faber, Ana J García-Sáez.
      The activator of apoptosis harakiri (HRK) is a pro-apoptotic BCL-2 homology 3 (BH3)-only protein of the apoptosis regulator Bcl-2 (BCL-2) family that is mainly expressed in neuronal and haematopoietic tissues. How specific HRK protein domains contribute to its pro-apoptotic function, and what other non-apoptotic roles HRK performs within cells, remain poorly understood. Here, we evaluated the apoptosis sensitivity, and mitochondrial shape and function of HCT116 human colorectal cells lacking all BH3-only proteins as well as all relevant BCL-2 proteins. By reconstituting individual BH3-only proteins on this genetic background, we observed that HRK induces apoptosis in a manner dependent on its BH3 domain, and the presence of the apoptosis regulator BAX and BCL-2 homologous antagonist/killer (BAK), but independent of its transmembrane domain. Intriguingly, HRK also causes mitochondrial aggregation without altering cristae structure or respiration. Although the BH3 domain is not required for mitochondrial reorganisation, we found that the transmembrane domain requires additional upstream amino acids for HRK mitochondrial localisation and reorganisation. These observations uncover a previously unknown role of HRK in modulating mitochondrial morphology that is independent of its BH3 domain and pro-death function.
    Keywords:  BH3; Harakiri; apoptosis; mitochondria; transmembrane
    DOI:  https://doi.org/10.1111/febs.70255
  3. Nat Med. 2025 Sep 12.
    Mending a mother's mitochondrial DNA.
    Mike May.
      
    DOI:  https://doi.org/10.1038/d41591-025-00056-2
  4. Nat Metab. 2025 Sep 09.
    Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism.
    Ran Liu, Zihan Zhang, Aye K Kyaw, Kariona A Grabińska, Hardik Shah, Hongying Shen.
      The essential cofactor coenzyme A (CoASH) and its thioester derivatives (acyl-CoAs) have pivotal roles in cellular metabolism. However, the mechanism by which different acyl-CoAs are accurately partitioned into different subcellular compartments to support site-specific reactions, and the physiological impact of such compartmentalization, remain poorly understood. Here, we report an optimized liquid chromatography-mass spectrometry-based pan-chain acyl-CoA extraction and profiling method that enables a robust detection of 33 cellular and 23 mitochondrial acyl-CoAs from cultured human cells. We reveal that SLC25A16 and SLC25A42 are critical for mitochondrial import of free CoASH. This CoASH import process supports an enriched mitochondrial CoA pool and CoA-dependent pathways in the matrix, including the high-flux TCA cycle and fatty acid oxidation. Despite a small fraction of the mitochondria-localized CoA synthase COASY, de novo CoA biosynthesis is primarily cytosolic and supports cytosolic lipid anabolism. This mitochondrial acyl-CoA compartmentalization enables a spatial regulation of anabolic and energy-related catabolic processes, which promises to shed light on pathophysiology in the inborn errors of CoA metabolism.
    DOI:  https://doi.org/10.1038/s42255-025-01358-y
  5. J Biol Chem. 2025 Sep 08. pii: S0021-9258(25)02545-1. [Epub ahead of print] 110693
    Defined media reveals the essential role of lipid scavenging in supporting cancer cell proliferation.
    Oliver J Newsom, Eric Zheng, Lucas B Sullivan.
      Fetal bovine serum (FBS) is an undefined additive that is ubiquitous to mammalian cell culture media and whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understanding of the environmental requirements fulfilled by FBS. Here, we use a combination of live-cell imaging and quantitative lipidomics to elucidate the role of serum in supporting proliferation. We show that serum provides consumed factors that enable proliferation, with serum metal and lipid components serving as crucial metabolic resources. Despite access to a wide range of lipid classes available in serum, we find albumin-bound lipids are the primary species consumed by cancer cells. Furthermore, we find that supplementing with additives that contain necessary metals and any of the albumin-associated lipid classes can obviate the FBS requirement for cancer cell proliferation. Using this defined system, we investigated cancer cell lipid consumption dynamics, finding that albumin-associated lipids are primarily consumed through a mass-action mechanism with minimal competition within or amongst lipid classes. We also find that lipid scavenging is a dominant lipid acquisition route and is necessary for cancer cell proliferation. This work therefore identifies metabolic contributions of serum and provides a framework for building defined culture systems that sustain cell proliferation without the undefined contributions of serum.
    DOI:  https://doi.org/10.1016/j.jbc.2025.110693
  6. Transl Oncol. 2025 Sep 05. pii: S1936-5233(25)00252-9. [Epub ahead of print]61 102521
    NDUFS8 facilitates hepatocellular carcinoma growth by enhancing mitochondrial function and escaping HUWE1-dependent degradation.
    Xuxia Zhu, Ping Lu, Liang Ji, Qingyu Liang.
       BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Although mitochondrial metabolism contributes to tumorigenesis, the specific roles of individual mitochondrial components remain unclear.NADH:ubiquinone oxidoreductase core subunit S8 (NDUFS8), a key subunit of mitochondrial complex I, has been implicated in non-hepatic malignancies, but its functional relevance in HCC is unknown.
    METHODS: We assessed NDUFS8 expression in HCC tissues and cell lines using TCGA datasets and patient specimens. Functional analyses-including mitochondrial assays, apoptosis, proliferation, and migration-were performed in NDUFS8-silenced, knockout, and overexpressing HCC cells. In vivo tumor growth was evaluated using xenograft mouse models. Mechanistically, mass spectrometry and immunoprecipitation identified HUWE1 as an E3 ligase responsible for NDUFS8 ubiquitination.
    RESULTS: NDUFS8 was significantly overexpressed in HCC tissues and cell lines, correlating with poor patient prognosis. NDUFS8 localized to mitochondria and promoted complex I activity and ATP production. Knockdown or knockout of NDUFS8 impaired mitochondrial function, increased ROS, disrupted redox homeostasis, induced apoptosis, and suppressed proliferation and migration of HCC cells. In contrast, NDUFS8 overexpression enhanced oncogenic behaviors. In vivo, NDUFS8 silencing via AAV delivery significantly inhibited xenograft growth and triggered apoptosis. Mechanistically, HUWE1 was identified as a specific E3 ligase that ubiquitinates NDUFS8 at lysine 88, regulating its stability.
    CONCLUSIONS: NDUFS8 is a mitochondrial regulator that promotes HCC progression through metabolic activation and is post-translationally modified by HUWE1. Targeting NDUFS8 or its regulatory axis may represent a promising therapeutic strategy for HCC.
    Keywords:  Apoptosis; HCC; Mitochondria; NDUFS8,HUWE1
    DOI:  https://doi.org/10.1016/j.tranon.2025.102521
  7. Biochim Biophys Acta Bioenerg. 2025 Sep 04. pii: S0005-2728(25)00037-4. [Epub ahead of print] 149571
    Mechanism of Na+ ions contribution to the generation and maintenance of a high inner membrane potential in mitochondria.
    Victor V Lemeshko.
      A recent revision of the chemiosmotic theory was reported by Hernansanz-Agustín and coauthors as a discovery that a Na+ gradient across the mitochondrial inner membrane equates with the H+ gradient and contributes up to half of the inner membrane potential, without an explanation of the possible underlying mechanism. Based on the experimental data of these and other authors, and performed biophysical estimations, I propose a mechanism by which both the reported fast-acting Na+/H+ exchanger, associated with the complex I of the respiratory chain, and Na+ electrodiffusion in the intracristae space and the matrix allow maintenance of a high membrane potential.
    Keywords:  Chemiosmotic theory; Energy coupling; Inner membrane potential; Mitochondria; Na(+)/H(+) antiport
    DOI:  https://doi.org/10.1016/j.bbabio.2025.149571
  8. Sci Adv. 2025 Sep 12. 11(37): eadt3873
    Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells.
    Kelly McCastlain, Catherine Welsh, Yonghui Ni, Liang Ding, Ti-Cheng Chang, Robert J Autry, Besian I Sejdiu, Qingfei Pan, Melissa Franco, Wenan Chen, Huiyun Wu, Veronica Gonzalez-Pena, Patrick Schreiner, Sasi Arunachalam, Joung Hyuck Joo, Samuel Brady, Jinghui Zhang, Charles Gawad, William E Evans, M Madan Babu, Konstantin Khrapko, Jiyang Yu, Gang Wu, Stanley Pounds, Mondira Kundu.
      Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA-where mutant and wild-type mtDNA coexist-complicates efforts to define its contribution to disease progression. In this study, bulk whole-genome sequencing of 637 matched tumor-normal samples from the Pediatric Cancer Genome Project revealed an enrichment of functionally impactful mtDNA variants in specific pediatric leukemia subtypes. Collectively, the results from single-cell sequencing of five diagnostic leukemia samples demonstrated that somatic mtDNA mutations can arise early in leukemogenesis and undergo positive selection during disease progression, achieving intermediate heteroplasmy-a "sweet spot" that balances mitochondrial dysfunction with cellular fitness. Network-based systems biology analyses link specific heteroplasmic mtDNA mutations to metabolic reprogramming and therapy resistance. We reveal somatic mtDNA mutations as a potential source of functional heterogeneity and cellular diversity among leukemic cells, influencing their fitness and shaping disease progression.
    DOI:  https://doi.org/10.1126/sciadv.adt3873
  9. Leukemia. 2025 Sep 10.
    PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias.
    Alessandra Zaza, Giuseppe Zardo, Cristina Banella, Sara Tucci, Elisabetta de Marinis, Martina Gentile, Serena Travaglini, Mariadomenica Divona, Tiziana Ottone, Germana Castelli, Anna Maria Cerio, Daniela F Angelini, Isabella Faraoni, Raffaele Palmieri, Paquale Niscola, Emanuele Ammatuna, Adriano Venditti, Clara Nervi, Maria Teresa Voso, Gianfranco Catalano, Nelida Ines Noguera.
      At present there is no metabolic characterization of acute promyelocytic leukemia (APL). Pathognomonic of APL, PML::RARα fusion protein rewires metabolic pathways to feed anabolic tumor cell's growth. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapies render APL the most curable subtype of AML, yet approximately 1% of cases are resistant and 5% relapse. We characterized the metabolic peculiarity and fuel requirement of PML::RARα expressing cells, to identify new targets for tailored therapies in resistant or relapsed APL patients. We analyzed cell metabolism in primary samples from seven APL patients, comparing them with normal CD34+ cells differentiated to promyelocyte and granulocyte, and different PML::RARα expressing cell lines. We show that the PML::RARα oncoprotein inhibits glycolysis, promotes tricarboxylic acid cycle (TCA), and favors long chain fatty acids (LCFA) catabolism. Targeting CD36 function, that promotes the cellular uptake of fatty acids to feed oxidative phosphorylation (OXPHOS), effectively restores sensitivity to ATO in NB4 ATO-resistant clones. Notably, our data demonstrate that glycolytic impairment via AKT inhibition by PML::RARα renders APL cells reliant on OXPHOS. This dependency confers high sensitivity to the VTX-AZA combination, suggesting the therapeutic efficacy of targeted combination treatment in resistant or relapsed APLs.
    DOI:  https://doi.org/10.1038/s41375-025-02738-9
  10. Int J Mol Sci. 2025 Aug 27. pii: 8301. [Epub ahead of print]26(17):
    Impact of Acute Myeloid Leukemia Cells on the Metabolic Function of Bone Marrow Mesenchymal Stem Cells.
    Helal Ahmed, Pradeep Kumar Patnana, Yahya S Al-Matary, Maren Fiori, Jan Vorwerk, Marah H Ahmad, Eva Dazert, Lorenz Oelschläger, Axel Künstner, Bertram Opalka, Nikolas von Bubnoff, Cyrus Khandanpour.
      Acute myeloid leukemia (AML) proliferation is significantly influenced by the interactions between leukemia blasts and the bone marrow (BM) microenvironment. Specifically, bone marrow mesenchymal stem cells (BMSCs) derived from AML patients (AML-MSCs) are known to support leukemia growth and facilitate disease progression. Studies have demonstrated that the transfer of mitochondria from MSCs to AML blasts not only aids in disease progression but also contributes to chemotherapy resistance. Furthermore, BM stromal cells can trigger a metabolic shift in malignant cells from mitochondrial respiration to glycolysis, which enhances both growth and chemo-resistance. This study focuses on identifying transcriptional and metabolic alterations in AML-MSCs to uncover potential targeted therapies for AML. We employed RNA sequencing and microarray analysis on MSCs cocultured with leukemic cells (MLL-AF9) and on MSCs isolated from both non-leukemic and MLL-AF9 leukemic mice. The Gene Set Enrichment Analysis (GSEA) indicated a significant downregulation of gene sets associated with oxidative phosphorylation and glycolysis in AML-MSCs. Furthermore, coculture of MSCs from wild-type mice (WT-MSCs) and a healthy donor individual (HD-MSCs) with AML cells demonstrated reduced oxidative phosphorylation and glycolysis. These metabolic changes were consistent in AML-MSCs derived from both leukemic mice and patients. Our results indicate that AML cells diminish the metabolic capacity of MSCs, specifically targeting oxidative phosphorylation and glycolysis. These findings suggest potential metabolic vulnerabilities that could be exploited to develop more effective therapeutic strategies for AML.
    Keywords:  acute myeloid leukemia; bone marrow mesenchymal stromal cell; metabolism
    DOI:  https://doi.org/10.3390/ijms26178301
  11. Cells. 2025 Aug 29. pii: 1343. [Epub ahead of print]14(17):
    The Combination of Ibrutinib with BH3 Mimetics or Dichloroacetate Is Effective in B-CLL.
    Joaquín Marco-Brualla, Oscar Gonzalo, Gemma Azaceta, Isabel Izquierdo, Luis Palomera, Martín Villalba, Isabel Marzo, Alberto Anel.
      Since its discovery, the BTK inhibitor ibrutinib has redefined the standard treatments for hematological cancers, such as chronic lymphocytic leukemia (CLL). However, concerns exist regarding its secondary effects in humans and its occasional lack of efficacy in certain malignancies. Therefore, combined therapies with ibrutinib have emerged as promising new approaches. In this study, we aimed to explore its therapeutic potential through different approaches. For this purpose, we combined this drug with the BH3 mimetics ABT-199 and ABT-737, which inhibit anti-apoptotic members of the Bcl-2 family, and with the PDK1 inhibitor dichloroacetate (DCA), respectively. As cell models, we used ex vivo samples from patients and also selected the in vitro CLL cell line Mec-1, generating two sub-lines overexpressing Bcl-XL and Mcl-1, a common feature in this cancer. Results demonstrated a synergistic effect for both approaches, in all tumor cells tested, for both cytostatic and cytotoxic effects. Mechanistically, the expression of Bcl-2-family proteins was explored, exhibiting increases in pro-apoptotic, but also in anti-apoptotic, proteins upon ibrutinib treatment and a relative increase in the amount of the pro-apoptotic protein PUMA after treatment with DCA. Our data provides new insights into combined therapies with ibrutinib for CLL, which further expands our knowledge and the potential of this drug for cancer treatment.
    Keywords:  B-CLL; BH3 mimetics; Bcl-XL; Mcl-1; dichloroacetate; ibrutinib
    DOI:  https://doi.org/10.3390/cells14171343
  12. Semin Hematol. 2025 Aug 14. pii: S0037-1963(25)00034-4. [Epub ahead of print]
    Menin inhibition for the treatment of acute leukemia.
    Daniela V Wenge, Scott A Armstrong.
      Menin inhibitors are emerging as targeted therapies for acute leukemias with high HOXA gene expression. These leukemias harbor mutations including KMT2A-rearrangements, NPM1c mutations, NUP98-fusions, UBTF tandem duplications and potentially others. Mechanistically, each of these oncoproteins depend on the KMT2A:Menin interaction to maintain critical gene expression. Several Menin inhibitors have entered clinical trials and have shown impressive efficacy in heavily pretreated patients with acute myeloid leukemia (AML). Revumenib received FDA approval for patients with relapsed or refractory acute myeloid leukemia with KMT2A-rearrangements in November 2024. Despite the success of Menin inhibitors, leukemia progression due to therapeutic resistance is a common occurrence with monotherapy. Hence, current clinical trials focus on Menin inhibition in combination with chemotherapy and/or standard-of-care targeted therapies to potentially overcome or prevent resistance. Menin inhibitors are also being investigated in patients with newly diagnosed acute leukemia or as a maintenance therapy post allogeneic stem cell transplantation. This review provides an overview of the mechanism of action of Menin inhibitors and the disease subsets that show sensitivity. We explain the current understanding of genetic resistance, mediated by Menin mutations that reduce drug binding affinity, and the emerging understanding of other types of resistance. Ongoing clinical trials are summarized, and we discuss the future role of Menin inhibition as a potentially practice-changing treatment for up to 50% of patients with AML.
    Keywords:  Acute leukemia; Clinical trials; Combination therapy; Drug resistance; Epigenetics; Menin inhibitors
    DOI:  https://doi.org/10.1053/j.seminhematol.2025.08.001
  13. Biomed Pharmacother. 2025 Sep 09. pii: S0753-3322(25)00724-3. [Epub ahead of print]191 118530
    The dual role of VDAC in cancer: Molecular mechanisms and advances in targeted therapy.
    Hongxia Huang, Min Chen, Shubing Feng, Zhenhong Lin, Yuanhang Liu.
      The voltage-dependent anion channel (VDAC) family proteins can be subdivided into three isoforms: VDAC1, VDAC2, and VDAC3. As core channels of the mitochondrial outer membrane, these proteins exhibit paradoxical regulatory roles in cancer development. This review systematically summarizes their structural and functional characteristics, as well as the contradictory mechanisms in tumorigenesis and progression.On the one hand, VDAC1 mediates channel closure by binding to the C-terminal tails (CTTs) of tubulins, enhances glycolysis through interaction with hexokinase to promote aerobic glycolysis (Warburg effect), stabilizes mitochondrial membrane potential, inhibits reactive oxygen species (ROS) production, and collaborates with the BNIP3/PINK1-Parkin pathway to regulate mitophagy, thereby facilitating tumor immune escape and metabolic adaptation. On the other hand, tubulin antagonists like erastin induce VDAC1/2 opening to reverse the Warburg effect, killing cancer cells via ferroptosis, and its oligomerization state can reverse apoptotic resistance. Advances in targeted therapy show that compounds based on VDAC gating regulation (such as avicin/acrolein for channel closure and erastin/betulinic acid for channel opening) exhibit significant antitumor effects in models of lung cancer, breast cancer, etc. Moreover, the interaction between TSPO and VDAC, as well as oligomerization regulation mediated by GPCPD1, have emerged as novel strategies.This review highlights the functional heterogeneity of VDAC isoforms and the challenges posed by ROS concentration thresholds for precision therapy, providing a theoretical basis for developing cancer treatment strategies targeting mitochondrial channels.
    Keywords:  Cancer metabolic reprogramming; Ferroptosis; Molecular mechanism; Targeted therapy; VDAC
    DOI:  https://doi.org/10.1016/j.biopha.2025.118530
  14. Leukemia. 2025 Sep 11.
    Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival.
    Farideh Miraki-Moud, Linda Ariza-McNaughton, Thinzar KoKo, Jad Othman, Randal Stronge, Johann de Bono, Nigel Russell, Ian Thomas, Amanda Gilkes, Alan Burnett, Leandro Rodrigues Santiago, Fay Cafferty, Leo Taussig, Allan Thornhill, Simon O'Connor, Dominique Bonnet, David C Taussig.
      Male sex is associated with worse outcome in acute myeloid leukemia (AML) in many studies. We analyzed the survival of 4281 patients treated with intensive chemotherapy in the AML17 and AML19 trials based on sex. Men had a significantly lower remission rate than women. Men had a higher incidence of adverse cytogenetic features and a lower incidence of the relatively favorable NPM1 mutation. However, male sex was an independent risk factor for survival in multi-variate analysis. We hypothesized that androgen signaling in men could worsen outcomes by protecting AML cells from chemotherapy. We demonstrated high levels of androgen receptor (AR) expression in AML across cytogenetic risk groups. We showed the AR expression was induced by IL-6 signaling in vitro and correlates with poor overall survival. Androgens had no effect on survival of primary AML cells in vitro, nor did they impact gene expression. Androgens did not protect AML cells against chemotherapy either in vitro or in vivo. Similar results were observed with estrogen signaling through estrogen receptor in vitro in AML cells. In conclusion, targeting the androgen pathway may not be a promising clinical strategy and sex hormone signaling in AML cells does not explain the poorer outcomes of men.
    DOI:  https://doi.org/10.1038/s41375-025-02752-x
This page is being maintained by Thomas Krichel. It was last updated on 2025‒09‒15 at 0:50.