Experimental Hematology & Oncology最新文献

{"title":"Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.","authors":"Pei-Wen Yang, Xin-Yi Xu, Ju-Ying Jiao, Feng-Jiao Wang, Zhen Chen","doi":"10.1186/s40164-026-00806-z","DOIUrl":"10.1186/s40164-026-00806-z","url":null,"abstract":"<p><p>Methionine is essential for protein synthesis and serves as a precursor to S-adenosylmethionine, supporting epigenetic modifications and cell growth. Unlike normal cells, cancer cells are dependent on methionine. Therapeutic strategies targeting metabolic vulnerability show promise but face challenges related to tumor heterogeneity and adaptive resistance, limiting clinical translation. This review comprehensively explores methionine metabolism in cancer, detailing its uptake, transport, and metabolic pathways that underpin tumor development. We examine tumor dependency on methionine across various cancer types and subtypes, highlighting oncogene-driven variability, including the pivotal roles of methionine adenosyltransferases (MATs), the methionine salvage enzyme 5'-methylthioadenosine phosphorylase (MTAP), and polyamine synthesis enzymes such as ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase 1 (AMD1). Epigenetic contributions involving DNA, RNA, and histone methylation are discussed, emphasizing their tissue-specific implications, such as the MATI/III:MATII ratio in liver cancer and methionine metabolic features in glioblastoma, including PET imaging applications. This review further addresses methionine metabolic plasticity within the tumor microenvironment, focusing on epigenetic and immune reprogramming, metabolic checkpoint regulation, and the role of methionine in tumor-initiating cells and cancer stem cells. Therapeutic strategies targeting methionine dependence, including dietary restriction, methioninase enzyme therapies, transporter inhibition, and combination regimens aimed at enhancing efficacy, are critically evaluated. Finally, we discuss current challenges and future directions, emphasizing the need for tumor-selective interventions, improved delivery systems, and personalized metabolic diagnostics to translate metabolic vulnerabilities into effective clinical cancer therapies. This integrated analysis underscores the potential of targeting methionine metabolism for advancing cancer treatment strategies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13422318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in antibody-drug conjugates in cancer: latest updates from the 2026 AACR annual meeting.","authors":"Yan-Ruide Li, Yichen Zhu, Yuning Chen","doi":"10.1186/s40164-026-00804-1","DOIUrl":"10.1186/s40164-026-00804-1","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are rapidly evolving from conventional cytotoxic delivery systems into multifunctional, immune-integrated therapeutic platforms. Highlights from the 2026 American Association for Cancer Research (AACR) Annual Meeting demonstrate significant advances in ADC design, including dual- and multi-payload constructs, multispecific targeting strategies, and immunostimulatory payloads. These innovations aim to overcome key limitations such as tumor heterogeneity, resistance, and systemic toxicity. Novel approaches targeting the tumor microenvironment, including depletion of regulatory T cells and tumor-associated macrophages, further expand the therapeutic scope of ADCs beyond direct tumor cell killing. In parallel, integration with emerging modalities such as engineered CD16-enhanced natural killer T (NKT) cells underscores the potential for synergy between ADCs and cellular immunotherapies. Advances in AI-guided target discovery and antibody engineering are also enhancing tumor selectivity and internalization. Collectively, these developments highlight a paradigm shift toward precision, multi-mechanistic ADCs with the potential to improve clinical outcomes across diverse cancer types.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging multimodal cancer immunotherapy to amplify the efficacy of oncolytic viruses.","authors":"Qiying Cai, Louqian Zhang, Lingkai Kong, Juan Fang, Juan Xu, Xiaosong Gu, Wujun Li, Chunping Jiang, Junhua Wu","doi":"10.1186/s40164-026-00805-0","DOIUrl":"10.1186/s40164-026-00805-0","url":null,"abstract":"<p><p>Oncolytic viruses (OVs) represent a versatile platform for cancer immunotherapy, capable of selectively infecting and lysing tumor cells while triggering systemic antitumor immunity. However, their therapeutic efficacy remains limited by antiviral immunity, restricted intratumoral spread, and an immunosuppressive tumor microenvironment. This review highlights emerging strategies to potentiate OV efficacy through rational combination with complementary immunotherapies, including immune checkpoint inhibitors, adoptive cell therapies, cancer vaccines, and small-molecule immunomodulators. These synergistic interventions can remodel the tumor microenvironment, enhance immune cell infiltration and activation, reverse immunosuppressive feedback, promote immunogenic cell death, normalize the tumor vasculature, and modulate the gut microbiota, collectively amplifying OV replication and oncolytic potency. The integration of artificial intelligence and multiomics profiling further enables precise patient stratification and optimization of combination regimens. In parallel, advanced engineering strategies, such as arming OVs with immunomodulatory transgenes and mitigating host antiviral responses, further reinforce these effects. Together, these approaches illustrate how multimodal immunotherapy can overcome the intrinsic limitations of OVs, enabling durable antitumor immunity. This review underscores the central role of combination strategies in OV-based immuno-oncology and outlines future directions to accelerate their clinical translation.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the cancer metabolism-immunity interface: update and perspectives.","authors":"Emma Di Carlo","doi":"10.1186/s40164-026-00776-2","DOIUrl":"10.1186/s40164-026-00776-2","url":null,"abstract":"<p><p>Metabolic crosstalk between cancer cells and immune cells is now recognized as a major determinant of immune escape and resistance to anticancer treatments. Cancer cells profoundly reshape the metabolic landscape of the tumor microenvironment, driving nutrient competition, hypoxia, and the accumulation of immunosuppressive oncometabolites that collectively blunt antitumor immunity. Effector T cells, NK cells, and dendritic cells are exposed to nutrient deprivation and suppressive metabolites, including lactate, adenosine, and kynurenine, resulting in impaired T cell proliferation and cytotoxic function and expansion of metabolically adapted regulatory T cells and myeloid-derived suppressor cells. Cancer-associated fibroblasts further reinforce this metabolic reprogramming through extracellular matrix remodeling, secretion of immunosuppressive metabolites, and nutrient recycling that supports tumor growth. Abnormal tumor vasculature sustains metabolic stress by causing uneven perfusion, hypoxia, and acidosis, thereby limiting immune cell infiltration, and promoting immune exhaustion. In addition, diet- and microbiome-driven metabolic cues dynamically shape cancer-immunity interactions and therapeutic responses. Targeting key metabolic checkpoints, including glycolysis, adenosine signaling, tryptophan metabolism, fatty acid oxidation, and lactate production, has emerged as a promising strategy to restore antitumor immunity. Nevertheless, metabolic heterogeneity, context-dependent immune responses, and safety concerns pose persistent challenges to its successful implementation. Recent advances in biomarker development, patient stratification, and rational combination strategies underpin the clinical translation of metabolic-immune vulnerabilities in cancer therapy. Integrating metabolic interventions with immune checkpoint blockade or adoptive cell therapies has demonstrated synergistic effects in preclinical and early clinical studies, enhancing T cell persistence and cytotoxic function within metabolically hostile tumor microenvironments. This review addresses these issues and delineates the mechanistic basis of the dynamic interplay between cancer metabolism and immune regulation. It discusses how anti-cancer therapies affect metabolic and immune pathways and highlights next-generation, metabolically targeted therapies that leverage newly uncovered, tumor-specific rewiring of glycolysis, mitochondrial function, and nutrient uptake. Special emphasis is given to the development of first-in-class inhibitors targeting glutaminase, lipid biosynthesis, one-carbon pathways, and redox homeostasis, which, when paired with immunotherapy or conventional treatments, offer unprecedented opportunities to overcome metabolic barriers, abrogate resistance, and achieve durable immune control of cancer.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized chemotherapy guidance using patient-derived scaffolds from peritoneal colorectal metastases.","authors":"Simona Salerno, André Holdfeldt, Anders Ståhlberg, Marianne Quiding Järbrink, Göran Landberg, Elinor Bexe Lindskog","doi":"10.1186/s40164-026-00801-4","DOIUrl":"10.1186/s40164-026-00801-4","url":null,"abstract":"<p><p>Peritoneal metastases from colorectal cancer are associated with poor survival and limited therapeutic efficacy. To model patient-specific treatment responses, we generated patient-derived scaffolds (PDS) through tumor decellularization, preserving critical microenvironmental features for functional ex vivo analysis. PDS from 75 metastases were recellularized with HT29 cells and treated with 5-fluorouracil (5-FU), mitomycin C, or oxaliplatin. Gene expression related to proliferation, epithelial phenotype, epithelial-mesenchymal transition, and stemness was quantified and integrated into a composite treatment score to estimate the most favorable therapy for each patient. Treatment responses were influenced by both drug exposure and the patient-specific microenvironment. Importantly, subcluster distributions differed across treatment arms, supporting the concept that therapeutic response is modulated by microenvironmental context rather than being solely drug dependent. These findings were supported in a smaller validation cohort using HCT116 and DLD-1 cells recellularized into selected PDS. Treatment scoring based on HT29 cells revealed heterogeneous sensitivity patterns, with 38.7% of PDS responding best to 5-FU, 36% to mitomycin C, and 25.3% to oxaliplatin. Patients with more than two favorable treatment scores had improved disease-free survival (p = 0.0415). The PDS platform enables functional profiling of chemotherapy-response and may support individualized treatment strategies for colorectal cancer patients with peritoneal metastases.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, efficacy, and pharmacokinetics of eratrectinib (VC004) in solid tumors with NTRK fusions: phase 1 results from a phase 1/2 study.","authors":"Shengyu Zhou, Changgong Zhang, Guowen Wang, Jun Qian, Gang Huang, Jiaqiang Wang, Suxia Luo, Youhua Zhu, Qingyuan Zhang, Ting Wei, Yongsheng Li, Zhendong Li, Dongyuan Zhu, Huarong Zhao, Meiyu Fang, Shoubing Zhou, Qing Xu, Yu Chen, Kejun Nan, Jiuwei Cui, Xueqiang Zhu, Yanchun Gong, Yong Wu, Xiaojuan Lai, Yuankai Shi","doi":"10.1186/s40164-026-00799-9","DOIUrl":"10.1186/s40164-026-00799-9","url":null,"abstract":"<p><strong>Background: </strong>Tropomyosin receptor kinases (TRK) tyrosine kinase inhibitors (TKIs) have demonstrated marked efficacy in neurotrophic receptor tyrosine kinase (NTRK) fusion positive tumors. However, resistance inevitably develops. Eratrectinib (VC004) is a next-generation selective TRK TKI which can overcome drug resistance.</p><p><strong>Methods: </strong>In this phase 1 study, patients with locally advanced or metastatic solid tumors were enrolled in the dose-escalation part. A standard 3 + 3 design was adopted to sequentially assign patients at 25 mg twice daily (BID), 50 mg BID, 100 mg BID, and 200 mg BID dose levels of oral eratrectinib. After each dose had been established, we expanded specific dose cohorts in patients with NTRK fusion positive locally advanced or metastatic solid tumors to obtain adequate data for safety, pharmacokinetics (PK), and efficacy. The primary endpoints of this study were safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).</p><p><strong>Results: </strong>Between December 4, 2020 and November 4, 2021, 16 patients were enrolled in the dose-escalation part and a dose of 100 mg BID was identified as MTD. Between May 8, 2021 and March 19, 2025, 75 patients were enrolled in the dose-expansion part at doses of eratrectinib 25 mg BID, 50 mg BID, and 75 mg BID. Treatment-emergent adverse events (TEAEs) occurred in 94.7% (71/75) of patients. The most common treatment-related adverse events (TRAEs) included dizziness (51/75, 68.0%), anaemia (28/75, 37.3%), weight increased (27/75, 36.0%), hypertriglyceridemia (25/75, 33.3%). ≥ grade 3 TRAEs occurred in 17.3% (13/75) of patients. No TRAEs led to death. The dose of 50 mg BID was chosen as RP2D based on the results of safety, PK, and efficacy. At the RP2D dose, objective response rate (ORR) was 70% (21/30, 95% confidence interval 50.6-85.3).</p><p><strong>Conlusions: </strong>Eratrectinib demonstrated manageable safety profile and promising efficacy in patients with NTRK fusion positive solid tumors, representing a new treatment option for this patient population. Further studies to confirm the efficacy and safety of eratrectinib are ongoing. Trial registration NCT04614740 (ClinicalTrials.gov).</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAGEC2 promotes tumorigenesis in multiple myeloma through USP16-mediated deubiquitination and stabilization of c-Myc.","authors":"Zihao Liu, Tingting Hu, Jie Min, Chen Wang, Yuhao Cao, Mengjie Guo, Jinjun Qian, Chunyan Gu, Ye Yang","doi":"10.1186/s40164-026-00782-4","DOIUrl":"10.1186/s40164-026-00782-4","url":null,"abstract":"<p><p>Multiple myeloma (MM) is an incurable malignancy characterized by clonal plasma cell proliferation, in which dysregulated ubiquitination plays a key pathogenic role. Using bufalin as a molecular probe, we identified melanoma-associated antigen C2 (MAGEC2) as a direct binding target and investigated its unconventional function beyond canonical E3 ligase modulation. MAGEC2 expression and clinical relevance were analyzed in patient cohorts. Functional assays (MTT, Western blot, CCK-8, flow cytometry) and mechanistic studies (co-immunoprecipitation, mass spectrometry, ubiquitination assays) were performed in vitro and in an adoptive B-cell transfer mouse model. High MAGEC2 expression was significantly associated with poor overall survival in MM patients. Functionally, MAGEC2 promoted malignant proliferation and induced resistance to adriamycin and bortezomib. Mechanistically, in addition to its known role in enhancing E3 ligase activity, MAGEC2 directly bound and increased the deubiquitinase activity of USP16, leading to c-Myc stabilization via reduced ubiquitination. Interactions among MAGEC2, USP16, and c-Myc were confirmed both in vitro and in vivo, establishing a MAGEC2-USP16-c-Myc axis. MAGEC2 overexpression also exacerbated bone lesions in vivo. Collectively, these findings identify MAGEC2 as both a prognostic biomarker and a promising therapeutic target in MM, and highlight its role as a multifunctional regulator of the ubiquitin system.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biology-informed risk stratification of glioblastoma by integrating MRI-based intratumoral heterogeneity with clinical features: a multicenter validation study.","authors":"Junfeng Zhang, Hong Guo, Xiaoxiao Ma, Yujue Zhong, Xiaojun Yu, Xiangbing Bian, Jianxing Hu, Caohui Duan, Yilong Huang, Jialing Wu, Mingliang Yang, Jian Hu, Xiaobo Zhang, Luhua Zhang, Rui Jiang, Xin Lou","doi":"10.1186/s40164-026-00788-y","DOIUrl":"10.1186/s40164-026-00788-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Refined risk stratification before randomization is clinically important for reducing prognostic imbalance across study arms when evaluating novel therapies for glioblastoma. However, current artificial intelligence-assisted prognostic models are often limited by complex computational pipelines, limited bedside applicability, and insufficient biological interpretability. This study aimed to develop a prognostic model, supported by an online-accessible platform, for individualized risk stratification of glioblastoma using MRI-based intratumoral heterogeneity and routinely available clinical features, and to investigate the biological meaning of model-driven risk stratification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective multicenter study included 836 patients with isocitrate dehydrogenase-wildtype glioblastoma from six centers between October 1996 and May 2025. The habitat risk score (HRS) for each patient was derived from a proposed intratumoral heterogeneity index and quantitative metrics extracted from three-dimensional preoperative MRI-based vascular habitat mappings. Independent predictors of overall survival (OS) were identified using Cox proportional hazards regression analysis, and three prognostic models (HRS model, clinical model, and radio-clinical model) were developed and validated in spatial and temporal external sets. Model interpretability was assessed using time-stratified Shapley additive explanations (SHAP) analysis. A web-based interactive platform was implemented for rapid individualized risk assessment. The biological meaning of model-driven risk stratification was explored using transcriptomic and histologic profiling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HRS, Karnofsky performance status (KPS), O&lt;sup&gt;6&lt;/sup&gt;-methylguanine-DNA methyltransferase promoter methylation status, and extent of resection were identified as independent predictors of OS, with KPS and HRS contributing most strongly to survival prediction in SHAP analysis. The radio-clinical model demonstrated good predictive performance and outperformed the clinical model and the HRS model, with C-indexes of 0.74 and 0.77 in the spatial and temporal validation sets, respectively. It also effectively stratified patients into low- and high-risk groups regardless of first-line therapeutic regimen (log-rank, P &lt; 0.05). Mechanistically, high-risk tumors showed increased tumor stemness and expanded HIF1α-positive regions, whereas low-risk tumors exhibited an immune-stimulatory phenotype. The deployed web-based platform enabled rapid patient-specific risk estimation to support bedside application.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study establishes an interpretable and clinically deployable framework for glioblastoma risk stratification by integrating imaging-derived intratumoral heterogeneity with routine clinical features, without requiring complex computational infrastructure. The model also provides biologically grounded insights ","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world evidence on infection risk in multiple myeloma treated with BiTEs and CAR-T cells: a meta-analysis.","authors":"Federico Spataro, Vanessa Desantis, Giuseppe Dicuonzo, Stefano Molica, Hermann Einsele, Angelo Vacca, Roberto Ria, Antonio Giovanni Solimando","doi":"10.1186/s40164-026-00798-w","DOIUrl":"10.1186/s40164-026-00798-w","url":null,"abstract":"<p><strong>Background: </strong>T-cell-redirecting therapies, including bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, have substantially improved outcomes in relapsed or refractory multiple myeloma (RRMM). However, infectious complications remain a major safety concern, particularly in real-world settings, where patients are more heterogeneous than those enrolled in clinical trials.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of real-world retrospective studies evaluating severe (grade 3-4) infections in adult patients with RRMM treated with approved BiTEs or CAR-T cell therapies. Pooled event rates were estimated using random-effects models. Heterogeneity was explored through subgroup analyses, meta-regression, and sensitivity analyses.</p><p><strong>Results: </strong>Sixteen studies encompassing 2,097 patients were included. Overall, 24.2% of patients developed grade 3-4 infections (pooled event rate 0.24; 95% CI, 0.21-0.28). Among BiTEs-treated patients (n = 1,602), the pooled severe infection rate was 0.26 (95% CI, 0.23-0.30), with higher rates observed for BCMA-directed BiTEs (0.27) compared with GPRC5D-directed BiTEs (0.25). CAR-T cell therapies (n = 495) were associated with a lower pooled infection rate (0.19; 95% CI, 0.12-0.27).</p><p><strong>Conclusions: </strong>In real-world practice, severe infections affect approximately one in four patients receiving T-cell-redirecting therapies for RRMM. Observed differences in infection rates across platforms and targets should be interpreted with caution, as they derive from indirect comparisons in non-randomized, heterogeneous cohorts. Nevertheless, these data support incorporating patient frailty and prior infection history into therapeutic decision-making. CAR-T therapy, or GPRC5D-directed BiTEs when CAR-T is not feasible, may represent reasonable options in patients at higher infectious risk, within an individualized and context-dependent treatment strategy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical research progress of menin inhibitors for acute myeloid leukemia: latest updates from the 2025 ASH Annual Meeting.","authors":"Chenchen Ma, Siyuan Cui, Jingyi Wang","doi":"10.1186/s40164-026-00803-2","DOIUrl":"10.1186/s40164-026-00803-2","url":null,"abstract":"<p><p>Menin inhibition has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML) driven by KMT2A rearrangements or NPM1 mutations. Novel menin inhibitors, including revumenib, bleximenib, ziftomenib, and enzomenib, are currently under clinical evaluation, and selected updated clinical results were presented at the 2025 American Society of Hematology (ASH) Annual Meeting. This brief review summarizes the key findings and discusses the emerging clinical questions regarding combination strategies, treatment sequencing, and molecularly defined use of menin inhibitors.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}