Molecular Oncology最新文献

{"title":"Evaluation of KRAS and NRAS mutations in metastatic colorectal cancer: an 8-year study of 10 754 patients in Turkey.","authors":"Gozde Kavgaci, Izzet Akiva, Yavuz Hakan Ozon, Hakan Berkil, Huseyin Karadayi, Omer Dizdar, Suayib Yalcin","doi":"10.1002/1878-0261.70042","DOIUrl":"https://doi.org/10.1002/1878-0261.70042","url":null,"abstract":"<p><p>This study aimed to evaluate KRAS and NRAS mutations over an eight-year period to provide a comprehensive understanding of the genetic landscape of metastatic colorectal cancer (mCRC) in Turkish patients. Tumor tissue samples were collected from 10 754 patients with mCRC between January 2015 and June 2023 from multiple centers across Turkey, and all genetic analyses were performed at a single facility. DNA was analyzed for mutations in codons 12, 13, 59, 61, 117, and 146 of the KRAS and NRAS genes using nested PCR and multiplex minisequencing techniques. Among the conclusive results from 10 681 patients, 46.6% (4982) had KRAS mutations, and 53.4% (5699) were wild-type. The most common KRAS mutations were G12D (30.3%), G12V (20.1%), G13D (18.4%), and G12C (7.0%). Results from the 5699 KRAS wild-type patients revealed that 480 (8.5%) had NRAS mutations, while 91.5% were NRAS wild-type. The most frequent NRAS mutations were Q61K (19.7%), G12D (19.1%), and G12V (12%). This study provides a large-scale, real-world dataset of KRAS and NRAS mutation profiles in Turkish mCRC patients, contributing significantly to the understanding of the genetic characteristics of mCRC in this population.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPM8 levels determine tumor vulnerability to channel agonists.","authors":"Alessandro Alaimo, Francesco Giuseppe Carbone, Kristi Buzo, Nicole Annesi, Sacha Genovesi, Annalisa Lorenzato, Karen Widmann, Michela Libergoli, Elisa Marmocchi, Giovanni Bertalot, Alberto Brolese, Mauro Giulio Papotti, Luca Molinaro, Orazio Caffo, Mattia Barbareschi, Alberto Bardelli, Alessandro Romanel, Sabrina Arena, Andrea Lunardi","doi":"10.1002/1878-0261.70049","DOIUrl":"https://doi.org/10.1002/1878-0261.70049","url":null,"abstract":"<p><p>Targeted therapies have pervasively enhanced clinical protocols and significantly improved survival and quality of life of cancer patients. Mostly grounded on small molecules and antibodies targeting deregulated mechanisms in cancer cells, precision oncology approaches are limited to a few tumor types because of the paucity of clinically actionable targets. Here, we report a comparative analysis of the cation channel transient receptor potential melastatin 8 (TRPM8; also known as transient receptor potential cation channel subfamily M member 8) in lung, breast, colorectal, and prostate cancers. Our findings reveal high levels of channel expression in cores of all four carcinomas, irrespective of reduced expression of its RNA. Importantly, cancer cell lines that represent the various tumor types consistently show that sub-lethal chemotherapy dosages combined with the TRPM8 agonist D-3263 have a synergistic lethal effect. In addition, administration of D-3263 increases the cytotoxicity of 5-FU/Oxaliplatin in patient-derived colorectal cancer organoids, depending on the levels of TRPM8. Overall, our study strengthens the candidacy of TRPM8 as a molecular target for precision oncology approaches and paves the way for the design of basket trials for its clinical testing in TRPM8-high tumors.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of proton-sensing GPR4 reduces tumor progression in mouse models of colon cancer.","authors":"Leonie Perren, Moana Busch, Pedro A Ruiz, Ermanno Malagola, Valeria Baumeler, Federica Foti, Adelina Gross, Tobias Grütter, Hendrik Edel, Cordelia Schuler, Kristina Handler, Glenn De Lange, Isabelle C Arnold, Cheryl de Vallière, Klaus Seuwen, Martin Hausmann, Gerhard Rogler","doi":"10.1002/1878-0261.70045","DOIUrl":"https://doi.org/10.1002/1878-0261.70045","url":null,"abstract":"<p><p>We aimed to understand the role of G protein-coupled receptor 4 (GPR4) in tumorigenesis. GPR4 is a pH-sensing receptor that is activated by acidic extracellular pH. GPR4 is expressed primarily in vascular endothelial cells (ECs). Intestinal tissue from patients with inflammatory bowel disease (IBD) shows increased expression of GPR4. Patients with IBD have a significantly increased risk of developing colorectal cancer (CRC). In the MC38 model, Gpr4-deficient mice showed significantly reduced tumor size and weight compared to wild-type (WT) mice. This effect correlated with a significant increase in IL2 protein and natural killer (NK)1.1⁺ cells in tumor tissue in Gpr4^-/- compared to WT. In the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of CRC, Gpr4-deficient mice showed significantly reduced tumor progression and number of apurinic/apyrimidinic (AP) sites. Gpr4-deficient mice showed a significantly increased number of NKp46⁺ cells in tumor tissue, and increased numbers of NK cells were confirmed by qPCR and flow cytometry. The absence of GPR4 significantly attenuated tumor progression in the colon of mice, and this result correlated with increased cytotoxic cell activity and reduced presence of tumor-associated macrophages and neutrophils. GPR4 represents a potential new target for therapeutic intervention.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of primary cilia promotes EphA2-mediated endothelial-to-mesenchymal transition in the ovarian tumor microenvironment.","authors":"Jin Gu Cho, Yubin Hah, Eunsik Yun, Hye In Ka, Aram Lee, Sora Han, Dawn Lee, Sung Wook Kim, Jong Hoon Park, Byung Su Kwon, Young Yang, Jongmin Kim","doi":"10.1002/1878-0261.70057","DOIUrl":"https://doi.org/10.1002/1878-0261.70057","url":null,"abstract":"<p><p>Endothelial-to-mesenchymal transition (EndMT) is closely associated with tumor progression. Endothelial cells (ECs) in the tumor microenvironment (TME) use EndMT programs to facilitate tumor progression; however, the underlying mechanisms in ovarian cancer are poorly understood. Here, we describe the involvement of primary cilia in EndMT of the ovarian TME. We showed that ECs from human ovarian tumors displayed robust EndMT and impaired cilia formation, as was also observed in ECs in response to ovarian cancer cell culture-conditioned media (OV-CM). Notably, ECs lacking primary cilia exhibited increased OV-CM-induced EndMT. Vascular abnormalities, such as enhanced cell migration and vessel permeability, were observed in vitro. Furthermore, in vivo experiments using endothelial-specific kinesin family member 3A (Kif3a)-knockout mice showed enhanced EndMT in the ovarian TME. Mechanistically, we identified ephrin type-A receptor 2 (EphA2) as a key regulator of EndMT. Upon OV-CM treatment, EphA2 expression increased, and depletion of EphA2 in ECs decreased OV-CM-induced EndMT and vascular abnormalities. These results highlight that the loss of primary cilia and the consequent EphA2 activation are key mechanisms by which EndMT programs induce the acquisition of cancer-associated fibroblast-like cells in the ovarian TME, thereby promoting ovarian cancer progression.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive omics-based classification system in adult patients with B-cell acute lymphoblastic leukemia.","authors":"Yang Song, Ting Liu, Qishan Hao, Qiuyun Fang, Xiaoyuan Gong, Yan Li, Zheng Tian, Hui Wei, Min Wang, Jianxiang Wang, Tao Cheng, Yingchang Mi","doi":"10.1002/1878-0261.70053","DOIUrl":"https://doi.org/10.1002/1878-0261.70053","url":null,"abstract":"<p><p>B-cell acute lymphoblastic leukemia (B-ALL) is a highly heterogeneous disease with a challenging prognosis, particularly in adult patients. We enrolled 88 adult B-ALL patients with transcriptomic and mutation profiles for classification system identification, and a comprehensive system for B-ALL patients (COMBAT) was developed. COMBAT stratified patients into three cohorts: (1) COMBAT1, characterized by high stem/myeloid antigen expression, low immune infiltration, high infiltration of endothelial cells, and hypo-CIMP (CpG island methylator phenotype); (2) COMBAT2, defined as an inflamed subtype with immune exhaustion, moderate myeloid antigen expression, and hypo-CIMP; and (3) COMBAT3, marked by proliferative profiles with MYC pathway activation and hypomethylation at enhancer regions in patients characterized by CIMP. The molecular features of the three COMBATs were verified in two external cohorts, the GSE34861 (N = 194) and GSE66005 (N = 109) datasets. In univariate analysis, only COMBAT classification presented significance for OS, and patients of COMBAT3 presented significantly superior survival than COMBAT1/2 in Ph-negative ALL. Ph-negative ALL patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the COMBAT3 group showed better overall survival (OS) than those in the COMBAT1-2 groups (estimated 3-year OS: 100% vs. 65.6%, P = 0.034), suggesting a prognostic benefit of this subtype. In summary, the COMBAT system redefines the characteristics of adult B-ALL subtypes and guides the selection of allo-HSCT for Ph-negative patients.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: lncRNA-PDPK2P Promotes Hepatocellular Carcinoma Progression Through the PDK1/AKT/Caspase 3 Pathway.","authors":"","doi":"10.1002/1878-0261.70044","DOIUrl":"https://doi.org/10.1002/1878-0261.70044","url":null,"abstract":"<p><strong>Retraction: </strong>W. Pan, W. Li, J. Zhao, Z. Huang, J. Zhao, S. Chen, C. Wang, Y. Xue, F. Huang, Q. Fang, J. Wang, D. Brand, and S. G. Zheng, \"lncRNA-PDPK2P Promotes Hepatocellular Carcinoma Progression Through the PDK1/AKT/Caspase 3 Pathway,\" Molecular Oncology 13, no. 10 (2019): 2246-2258, https://doi.org/10.1002/1878-0261.12553. The above article, published online on 01 August 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin Ryan; FEBS Press; and John Wiley & Sons Ltd. A third party reported to the journal that the one of the P-PDPK2P tumor images in Figure 2E appeared to exceed 2 cm in diameter, which exceeds the maximum size recommended by ARRIVE guidelines. Further investigation by the journal and the publisher also found evidence that the second and third P-NC mice in Figures 2E and 2F appeared to be the same mouse, although both were reported as having received different treatments. The authors responded to an inquiry by the publisher and provided original data. An evaluation of these data by the publisher further determined that there were several discrepancies between what was shown in the original data and what was reported in the published article. The authors stated that no mice had been reused between the images in Figures 2E and 2F. The authors also confirmed that one tumor image in Figure 2E exceeded 2 cm, but that the research was performed at the Third Affiliated Hospital at the Sun Yat-sen University and was in compliance with China's \"Guideline for Welfare and Ethical Review of Laboratory Animals\" (GB/T 35892-2018), which sets no tumor diameter limits for nude mice. The parties have determined that the authors violated ARRIVE guidelines governing the maximum size of tumor samples, which had been adopted by the journal at the time of submission. The parties have also determined that there is overwhelming evidence that two mouse subjects were reused in Figures 2E and 2F but were presented as having received different treatments. There were several other discrepancies between the original data provided by the authors and those presented in the published article. The retraction has been agreed to because the article did not conform to the ethical guidelines of the journal at the time of submission and because there is significant evidence that some data included in the article were inaccurate or misreported, which fundamentally compromises the editors' confidence in the conclusions presented. The authors did not indicate their agreement with the retraction.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-treatment dynamics of circulating extracellular vesicles in the first-line setting of patients with advanced non-small cell lung cancer: the LEXOVE prospective study.","authors":"Valerio Gristina, Viviana Bazan, Nadia Barraco, Simona Taverna, Mauro Manno, Samuele Raccosta, Anna Paola Carreca, Marco Bono, Tancredi Didier Bazan Russo, Francesco Pepe, Pasquale Pisapia, Lorena Incorvaia, Giuseppe Badalamenti, Giancarlo Troncone, Umberto Malapelle, Daniele Santini, Antonio Russo, Antonio Galvano","doi":"10.1002/1878-0261.13737","DOIUrl":"10.1002/1878-0261.13737","url":null,"abstract":"<p><p>Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non-small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum-based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell-free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z-averaged hydrodynamic diameter and polydispersity index. A total of 135 plasma samples from 27 patients were collected at baseline (T0) and at the first radiological restaging (T1). A ∆cfEV < 20% was associated with improved median progression-free survival (mPFS) in responders versus non-responders. Specifically, cfEV responders on pembrolizumab had a significantly better mPFS (25.2 months) compared to those on chemotherapy plus pembrolizumab (6.1 months). EGFR-positive cfEV responders also experienced longer mPFS compared to cfEV non-responders (35.1 months, 95% CI: 14.9-35.5 vs. 20.8 months, 95% CI: 11.2-30.4). This study suggested that monitoring circulating EV could provide valuable insights into treatment efficacy in NSCLC, particularly for patients receiving pembrolizumab or osimertinib.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1422-1435"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood leukocyte signatures as biomarkers in relapsed ovarian cancer patients receiving combined anti-CD73/anti-PD-L1 immunotherapy in arm A of the NSGO-OV-UMB1/ENGOT-OV30 trial.","authors":"Luka Tandaric, Annika Auranen, Katrin Kleinmanns, René DePont Christensen, Liv Cecilie Vestrheim Thomsen, Cara Ellen Wogsland, Emmet McCormack, Johanna Mäenpää, Kristine Madsen, Karen Stampe Petersson, Mansoor Raza Mirza, Line Bjørge","doi":"10.1002/1878-0261.13811","DOIUrl":"10.1002/1878-0261.13811","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have demonstrated limited efficacy in overcoming immunosuppression in patients with epithelial ovarian cancer (EOC). Although certain patients experience long-term treatment benefit, reliable biomarkers for responder pre-selection and the distinction of dominant immunosuppressive mechanisms have yet to be identified. Here, we used a 40-marker suspension mass cytometry panel to comprehensively phenotype peripheral blood leukocytes sampled over time from patients with relapsed EOC who underwent combination oleclumab (anti-CD73) and durvalumab (anti-PD-L1) immunotherapy in the NSGO-OV-UMB1/ENGOT-OV30 trial. We found that survival duration was impacted by baseline abundances of total peripheral blood mononuclear cells. Longitudinal analyses revealed a significant increase in CD14⁺CD16^- myeloid cells during treatment, with significant expansion of monocytic myeloid-derived suppressor cells occurring in patients with shorter progression-free survival, who additionally showed a continuous decrease in central memory T-cell abundances. All patients demonstrated significant PD-L1 upregulation over time on most T-cell subsets. Higher CD73 and IDO1 expression on certain leukocytes at baseline significantly positively correlated with longer progression-free survival. Overall, our study proposes potential biomarkers for EOC immunotherapy personalization and response monitoring; however, further validation in larger studies is needed.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1436-1451"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.","authors":"Tessa S Seale, Li Li, J Kyle Bruner, Melody Chou, Bao Nguyen, Jaesung Seo, Ruiqi Zhu, Mark J Levis, Christine A Pratilas, Donald Small","doi":"10.1002/1878-0261.13749","DOIUrl":"10.1002/1878-0261.13749","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) patients with the FMS-related receptor tyrosine kinase 3 internal tandem duplication (FLT3/ITD) mutation have a poorer prognosis, and treatment with FLT3 tyrosine kinase inhibitors (TKIs) has been hindered by resistance mechanisms. One such mechanism is known as adaptive resistance, in which downstream signaling pathways are reactivated after initial inhibition. Past work has shown that FLT3/ITD cells undergo adaptive resistance through the reactivation of extracellular signal-regulated kinase (ERK) signaling within 24 h of sustained FLT3 inhibition. We investigated the mechanism(s) responsible for this ERK reactivation and hypothesized that targeting tyrosine-protein kinase receptor UFO (AXL), another receptor tyrosine kinase that has been implicated in cancer resistance, may overcome the adaptive ERK reactivation. Experiments revealed that AXL is upregulated and activated in FLT3/ITD cell lines mere hours after commencing TKI treatment. AXL inhibition combined with FLT3 inhibition to decrease the ERK signal rebound and to exert greater anti-leukemia effects than with either treatment alone. Finally, we observed that TKI-induced AXL upregulation occurs in patient samples, and combined inhibition of both AXL and FLT3 increased efficacy in our in vivo models. Taken together, these data suggest that AXL plays a role in adaptive resistance in FLT3/ITD AML and that combined AXL and FLT3 inhibition might improve FLT3/ITD AML patient outcomes.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1386-1403"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation.","authors":"Daniel Busa, Zdenka Herudkova, Jan Hyl, Jakub Vlazny, Filip Sokol, Kvetoslava Matulova, Adam Folta, Jakub Hynst, Lucy Vojtova, Leos Kren, Martin Repko, Zdenek Racil, Jiri Mayer, Martin Culen","doi":"10.1002/1878-0261.13790","DOIUrl":"10.1002/1878-0261.13790","url":null,"abstract":"<p><p>Patient-derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment. We compared seven biomaterials, which included both published and custom-designed materials. The highest level of bone marrow niche was achieved with extracellular matrix gels and custom collagen fiber, both of which allowed for a simple non-surgical implantation. The biomaterial selection did not influence the following AML infiltration. Regarding xenotransplantation, standard intravenous administration produced the most robust engraftment, even for two out of four otherwise non-engrafting AML samples. In contrast, direct intra-scaffold xenotransplantation did not offer any advantage. In summary, we demonstrate that the combination of an injectable biomaterial for scaffold creation plus an intravenous route for AML xenotransplantation provide the most convenient and robust approach to produce AML PDX using a humanized niche.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1371-1385"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}