Journal of Hematology & Oncology最新文献

{"title":"Vibecotamab for measurable residual disease in acute myeloid leukemia and for myelodysplastic syndromes and chronic myelomonocytic leukemia after hypomethylating agent failure: a phase II study.","authors":"Nicholas J Short,Alex Bataller,Courtney D DiNardo,Guillermo Montalban-Bravo,Sa A Wang,Wei Wang,Abhishek Maiti,Daniel Nguyen,Maria C Hachem,Timothy M Bi,Ghayas C Issa,Kelly S Chien,Maro Ohanian,Tapan M Kadia,Sanam Loghavi,Omer Karrar,Pavan Bachireddy,Hyunsoo Hwang,Xuelin Huang,Guillermo Garcia-Manero,Farhad Ravandi","doi":"10.1186/s13045-026-01825-3","DOIUrl":"https://doi.org/10.1186/s13045-026-01825-3","url":null,"abstract":"BACKGROUNDAcute myeloid leukemia (AML) with persistent measurable residual disease (MRD) and relapsed/refractory myelodysplastic syndromes (MDS) are low-blast myeloid diseases for which there are few effective therapeutic options. CD123 represents an attractive target in these diseases. Vibecotamab is a bispecific antibody that binds to CD123 on malignant blasts and to CD3 on T-cells, to recognize and eliminate CD123-positive malignant cells.METHODSThis single-center phase II study evaluated the efficacy of vibecotamab in patients AML with detectable MRD (AML-MRD cohort) or with MDS or chronic myelomonocytic leukemia (CMML) after hypomethylating agent failure (MDS/CMML cohort). In cycle 1, patients received vibecotamab IV on day 1 (0.43 µg/kg), day 3 (0.75 µg/kg), day 5 (1.1 µg/kg), and days 8, 15 and 22 (1.7 µg/kg). In subsequent cycles, patients received vibecotamab IV on days 1, 8, 15, and 22 (1.7 µg/kg). The primary outcomes were MRD negativity rate (AML-MRD cohort) and overall response (MDS/CMML cohort).RESULTSBetween May 2022 and April 2025, 48 patients were enrolled (21 AML-MRD cohort, 27 MDS/CMML cohort). The median ages of the AML-MRD and the MDS/CMML cohorts were 70 and 76 years, respectively. In the AML-MRD cohort, the median MRD level by flow cytometry was 0.64% (range, 0.1-3.9%), and in the MDS/CMML, the median bone marrow blast percentage was 7% (range, 3-19%). The AML-MRD clearance rate was 19% (4/21; 95% CI 5-42%), and in the MDS/CMML cohort, the overall response rate was 67% (18/27; 95% CI 46-83%). The median overall survival was 13.1 months (95% CI 8.9-NR) for the AML-MRD cohort and 6.5 months (95% CI 4.2-10.3) for the MDS/CMML cohort. The most frequent adverse event was infusion reaction or cytokine relapse syndrome, which occurred in 29 patients (60%) overall, most of which were grade 1-2.CONCLUSIONSVibecotamab was active in low-blast myeloid diseases, although the durability of responses was modest. Additional studies of CD123-targeting bispecific antibodies, alone or in combination, are warranted for these diseases.TRIAL REGISTRATIONClinicaltrials.gov (NCT05285813).","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"29 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148336214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes and prognostic factors in patients with systemic mastocytosis and an associated myeloid neoplasm: an international ECNM registry study.","authors":"Olivier Hermine,Orianne Debeaupuis,Gandhi Damaj,Johannes Lübke,Juliana Schwaab,Marc Heizmann,Frank Siebenhaar,Polina Pyatilova,Nicole Nojarov,Marek Niedoszytko,Aleksandra Gorska,Mattias Mattsson,Khalid Shoumariyeh,Stephan de Bra,Friederike Wortmann,Nikolas von Bubnoff,Horia Bumbea,Delia Soare,Chiara Elena,Judit Várkonyi,Anna Belloni Fortina,Simge Erdem,Knut Brockow,Tobias Michael Franz,Jens Panse,Deborah Christen,Christine Breynaert,Akif Selim Yavuz,Luca Malcovati,Michael Doubek,Vito Sabato,Ilaria Tanasi,Massimiliano Bonifacio,Karin Hartmann,Axel Rüfer,Mariarita Sciumè,Valentina Bellani,Irena Angelova-Fischer,Alex Stefan,Massimo Triggiani,Roberta Parente,Saskia K Klein,Michael Makris,Sotirios Papageorgiou,Paul van Daele,Ingunn Dybedal,Daniel Baffoe,Theo Gülen,Madlen Jentzsch,Olivier Lortholary,Mael Heiblig,Cristina Bulai Livideanu,Stéphane Barete,Clément Gourguechon,Sophie Dimicoli-Salazar,Olivier Tournilhac,Laurent Frenzel,Michel Arock,Andrzej Mital,Johannes N Woltsche,Hanneke C Kluin-Nelemans,Joanna N G Oude Elberink,Jason Gotlib,Martina Sperr,Andreas Reiter,Peter Valent,Wolfgang R Sperr,Julien Rossignol","doi":"10.1186/s13045-026-01819-1","DOIUrl":"https://doi.org/10.1186/s13045-026-01819-1","url":null,"abstract":"BACKGROUNDSystemic mastocytosis (SM) is a spectrum of hematologic disorders characterized by accumulation of atypical mast cells (MCs) in extracutaneous organs. SM with an associated hematologic neoplasm (SM-AHN), the most frequent subtype of advanced SM, is predominantly associated with myeloid neoplasms, consistent with shared clonal architecture. Because of its rarity and heterogeneity, robust outcome data aligned with contemporary classifications are needed to inform risk stratification.METHODSWe analyzed the 10th data wave of the European Competence Network on Mastocytosis registry (34 European centers and 1 US center). SM and AHN diagnoses followed the 2022 World Health Organization classification. Baseline characteristics and overall survival (OS) were compared between patients with myeloid SM-AHN and SM without AHN (SM-no-AHN). Within SM-AHN, outcomes were analyzed by SM component (advanced: aggressive SM [ASM] or MC leukemia [MCL] vs. non-advanced: bone marrow mastocytosis, indolent SM, or smoldering SM) and AHN subtype.RESULTSAmong 3,925 patients with SM, 467 (11.9%) had myeloid SM-AHN. Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) were the most frequent AHN category (41.1%), with chronic myelomonocytic leukemia as the most common subtype (29.6%). Compared with SM-no-AHN, SM-AHN patients were older, more often male, and less frequently had skin involvement. The SM component was advanced in 55.0% of SM-AHN versus 5.8% of SM-no-AHN (p < 0.001). OS was shorter in SM-AHN than SM-no-AHN (median 36.1 vs. 340.9 months; p < 0.001) and was reduced across SM subtypes, including ASM (31.0 vs. 81.1 months) and MCL (7.1 vs. 23.2 months). Within SM-AHN, advanced SM-AHN had shorter OS than non-advanced SM-AHN (28.3 vs. 70.9 months; p < 0.001). Median OS differed by AHN subtype (57.0 months in SM-MPN, 35.7 in SM-MDS, 34.2 in SM-MDS/MPN, and 14.7 in SM associated with acute myeloid leukemia; p < 0.001). In multivariable analysis, non-advanced SM (vs. advanced) remained independently associated with improved OS (hazard ratio = 0.44; p < 0.001).CONCLUSIONSSM-AHN is associated with reduced survival compared with SM without AHN across SM subtypes. Outcomes in SM-AHN are driven primarily by the aggressiveness of the mastocytosis component, supporting recognition and classification of SM in patients with concomitant myeloid neoplasms, given approved KIT-targeted tyrosine kinase inhibitors for advanced SM.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"22 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148336023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DAPK3-DCAF1 pathway regulates ZBP1 protein stability to orchestrate PANoptosis for ovarian cancer therapy.","authors":"Zhiqi Liao,Linghui Wang,Ziyan Zhang,Wenjian Gong,Mengshi Luo,Yuewen Zhang,Qiuyang Xu,Yijie Wu,Shennan Shi,Fan Xiong,Li Zhu,Xuejiao Zhao,Gordon B Mills,Ding Ma,Dan Liu,Guang-Nian Zhao,Qinglei Gao,Yong Fang","doi":"10.1186/s13045-026-01820-8","DOIUrl":"https://doi.org/10.1186/s13045-026-01820-8","url":null,"abstract":"BACKGROUNDOvarian cancer is characterized by an immunosuppressive \"cold\" tumor microenvironment, which poses a major challenge to effective therapy. Inducing immunogenic cell death through PANoptosis represents a promising strategy for remodeling the tumor microenvironment. Z-DNA binding protein 1 (ZBP1), an interferon (IFN)-stimulated gene, is a key sensor of Z-conformation nucleic acids (Z-NA) driving PANoptosis. While ZBP1 upregulation is traditionally attributed to transcriptional induction, its early non-transcriptional regulatory mechanisms remain elusive.METHODSZBP1 expression and its prognostic value were analyzed using public databases and clinical cohorts. APEX2 proximity labeling, PLA and Co-IP identified the E3 ubiquitin ligase regulating ZBP1. The IFN-mediated ZBP1 post-translational modification pathway was delineated utilizing PLA, Co-IP, in vitro phosphorylation, mutagenesis assays, an intestine-specific conditional knockout model. DCAF1-/- ovarian cancer cells and immunocompetent ID8 peritoneal models were generated to evaluate tumor growth and cell death. The therapeutic efficacy of combining the DCAF1 inhibitor (B32B3) with the Z-NA inducer (CBL0137) was assessed in an immunocompetent ID8 murine peritoneal tumor model and two chemoresistant patient-derived xenograft (PDX) models.RESULTSZBP1 is significantly downregulated in ovarian cancer, whereas its elevated expression predicts a favorable prognosis and correlates with high IFN responsiveness. Type I IFN triggers a rapid accumulation of ZBP1 protein prior to its transcriptional upregulation. Mechanistically, we identified the E3 ligase substrate receptor DCAF1 as a negative regulator that targets ZBP1 for proteasomal degradation. Interferon signaling activates the kinase DAPK3, which phosphorylates DCAF1 at S1328. This phosphorylation event compromises the assembly of the CRL4DCAF1 complex, thereby abrogating DCAF1-mediated degradation of ZBP1. In ovarian cancer models, genetic ablation of DCAF1 restored ZBP1 levels and significantly restrained tumor progression. Therapeutically, combining B32B3 with CBL0137 elevated intracellular Z-NA and stabilized ZBP1, driving PANoptosis and suppressing ovarian tumor growth across.CONCLUSIONSOur study identifies the IFN-DAPK3-DCAF1 pathway as a critical post-translational mechanism that ensures rapid ZBP1 stabilization. This highlights a fundamental strategy to bypass transcriptional latency for the rapid activation of immune responses, offering a strong clinical rationale to harness this pathway to induce ZBP1-dependent PANoptosis for the treatment of refractory tumors.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"195 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BTKi orelabrutinib improved the outcome of newly-diagnosed PCNS-LBCL by alleviating MyD88^L265P-induced PIM1 stability.","authors":"Yan Yuan, Bo Dai, Haoshu Zhong, Jiajun Zheng, Zhen Fan, Di Chen, Qian Wang, Hao Wu, Yuan Li, Ping Zhu, Tianling Ding, Shu Wang, Kunpeng Wu, Yu Zhang, Zhenhua Wang, Rui Feng, Fengping Zhu, Kang Zheng, Zhiyong Qin, Bojie Yang, Hong Chen, Xiaolei Lin, Yu Yao, Dongxiao Zhuang, Zhifeng Shi, Ying Mao, Tong Chen","doi":"10.1186/s13045-026-01812-8","DOIUrl":"10.1186/s13045-026-01812-8","url":null,"abstract":"<p><p>Primary central nervous system large B-cell lymphoma (PCNS-LBCL) exhibits the worst prognosis among all extranodal LBCLs, with the enriched genetic mutations in MyD88^L265P, CD79B and PIM1. However, the upfront incorporation of targeted therapies remains an unmet need in newly diagnosed (ND) patients. In this study, we found that in the presence of MyD88^L265P context, B-cell receptor downstream bruton's tyrosine kinase (BTK) was significantly overexpressed, which subsequently enhanced the stability of PIM1 oncoprotein. To evaluate the intracranial delivery of BTK inhibitor(BTKi), patient-derived PCNS-LBCL xenografted mice models were treated with highly-selective BTKi orelabrutinib, either monotherapeutically or in combining with methotrexate. Interestingly, orelabrutinib showed excellent efficiency crossing BBB with the functional BTK blockade and promoted PIM1 degradation, providing the molecular basis of incorporating BTKi into PCNS-LBCL therapy. Thus, we determined the efficacy and toxicity of orelabrutinib in combination with high-dose methotrexate in a prospective dose-escalating cohort and real-world practice. The patients being treated with orelabrutinib-included ORMD regimen showed better response and more prolonged survival compared to those with RMD regimen. We further investigated the genetic mutations of PCNS-LBCL across tumor tissue, cerebrospinal fluid (CSF) and plasma. The mutations in CSF circulating tumor DNA (ctDNA) rather than plasma-ctDNA were more consistent to those in tumor tissue, indicating that CSF-ctDNA is a useful tool for monitoring PCNS-LBCL. In summary, our data provided the molecular rationale as well as clinical evidences that incorporation of BTKi into frontline induction therapy is a promising strategy for ND PCNS-LBCL.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271545","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":"Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.","authors":"Haijia Tang, Youyang Shi, Qintao Ge, Rui Wang, Jianfeng Yang, Yao Zhu, Sheng Liu, Wenhao Xu","doi":"10.1186/s13045-026-01814-6","DOIUrl":"10.1186/s13045-026-01814-6","url":null,"abstract":"<p><p>Tumor immunity is shaped not only by the cellular composition of the tumor microenvironment (TME), but also by how stromal and immune elements are spatially organized within it. Among these regulators, cancer-associated fibroblasts (CAFs) and tertiary lymphoid structures (TLS) have emerged as two major determinants of the spatial niche of anti-tumor immunity. CAFs comprise heterogeneous and plastic stromal populations that can remodel the extracellular matrix, restrict lymphocyte infiltration, sustain chronic inflammation, and promote therapeutic resistance, while selected subsets may also support antigen presentation and lymphoid organization. In contrast, TLS function as ectopic immune hubs that coordinate local T- and B-cell priming, clonal expansion, and B-cell maturation, and are increasingly associated with favorable prognosis and improved responses to immune checkpoint blockade. In this review, we synthesize recent advances from single-cell and spatial multi-omics studies to examine how CAF states and TLS maturation programs arise, interact, and remodel the immune landscape across tumor types. We propose that the balance between CAF-driven stromal restriction and TLS-associated immune organization is a central determinant of immune exclusion versus immune activation. We discuss how this spatial framework may refine tumor classification, improve patient stratification, and guide therapeutic strategies aimed at stromal reprogramming, TLS induction or maturation, and rational combination immunotherapy, while highlighting innate immune-stromal circuits, including IL-33-activated ILC2s, NCR⁺ ILC3s, LTi-like programs, and myeloid organizer cells, as upstream regulators of TLS neogenesis. By integrating CAF biology, TLS dynamics, and spatial context, this review provides a conceptual framework for understanding and targeting the stromal architecture of tumor immunity.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271591","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":"Final analysis of phase 2 clinical trial of ruxolitinib and azacitidine combination therapy in patients with myelodysplastic syndrome/myeloproliferative neoplasms.","authors":"Sankalp Arora, Jayastu Senapati, Indraneel Deshmukh, Prithviraj Bose, Lucia Masarova, Sanam Loghavi, Xuemei Wang, Graciela Nogueras-Gonzalez, Guillermo Montalban-Bravo, Gautam Borthakur, Courtney D DiNardo, Tapan Kadia, Lingsha Zhou, Dyana Saenz, Habiba Halim, Yesid Alvarado, Maro Ohanian, Koichi Takahashi, Nicholas J Short, Elias Jabbour, Farhad Ravandi, Guillermo Garcia-Manero, Naveen Pemmaraju, Naval G Daver","doi":"10.1186/s13045-026-01813-7","DOIUrl":"10.1186/s13045-026-01813-7","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndrome and myeloproliferative neoplasm (MDS/MPN) overlap syndromes are characterized by the presence of features of both MDS and MPN and have a poor prognosis. We conducted a phase 2 clinical trial evaluating the combination of Azacitidine (AZA) and Ruxolitinib (RUX) in MDS/MPN, with interim analysis showing an objective response rate of 57%. Herein, we report the final analysis from this clinical trial, including long-term survival data.</p><p><strong>Methods: </strong>This was an open-label phase 2 clinical trial including adult patients in 2 diagnostic arms: myelofibrosis (arm 1) and MDS/MPN (arm 2). This manuscript reports outcomes of MDS/MPN patients. RUX 5-20 mg twice daily (per RUX label) was administered in 28-day cycles, and AZA 25 mg/m² on days 1-5 was added starting cycle 4. Primary endpoint was objective response rate per the 2015 International Consortium Proposal (ICP) MDS/MPN response criteria.</p><p><strong>Results: </strong>From 5/2013 to 8/2022, 52 patients were treated with a median age of 68 years (range, 39-82). Disease subtypes were MDS/MPN-Unclassifiable in 24 patients (46%), chronic myelomonocytic leukemia in 23 patients (44%), and atypical chronic myeloid leukemia in 5 patients (10%). Majority of patients (n = 40, 77%) had intermediate-2/high-risk disease by Dynamic International Prognosis Scoring System criteria. Objective responses were attained in 30 patients (58%), with a median duration of response of 13.6 months (95% CI: 6.4-41.1). After a median follow up of 88.5 months, 13 (25%) patients are alive, with median overall survival (OS) of 26.7 months (95% CI: 16.5-52.7), 5-year OS 33%. Median OS in MDS/MPN-U and CMML was 52.7 months (5-year OS 46%) and 17.5 months (5-year OS 27%), respectively. Twelve patients (23%) underwent allogeneic stem cell transplantation; with median OS not reached, 5-year OS 51%. Transformation to acute myeloid leukemia occurred in 13 patients (25%). The most common grade 3-5 adverse events (AEs) regardless of attribution were anemia (31, 60%), thrombocytopenia (27, 52%) and pneumonia (17, 33%). AE-related treatment discontinuation occurred in only 3 patients (6%).</p><p><strong>Conclusions: </strong>AZA-RUX therapy led to durable responses and encouraging OS in MDS/MPN with a manageable safety profile.</p><p><strong>Trial registration: </strong>NCT01787487, (clinicaltrials.gov, date: 2/6/2013).</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264824","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":"Luspatercept and imetelstat for myelodysplastic syndrome: updates from ASH 2025 annual meeting.","authors":"Yagya Ahlawat, Heng Jiang, Delong Liu","doi":"10.1186/s13045-026-01815-5","DOIUrl":"10.1186/s13045-026-01815-5","url":null,"abstract":"<p><p>Luspatercept, an erythroid maturation agent, and imetelstat, a first-in-class telomerase inhibitor, have expanded the therapeutic landscape for patients with myelodysplastic neoplasms (MDS). Recent data presented at the 2025 American Society of Hematology (ASH) Annual Meeting further clarify their evolving clinical roles. New analyses evaluated the real-world use of luspatercept in patients with lower-risk MDS (LR-MDS), while additional studies characterized the efficacy and outcomes associated with imetelstat in transfusion-dependent (TD) LR-MDS and in advanced MDS or acute myeloid leukemia following hypomethylating agent failure. We summarized the latest updates on luspatercept and imetelstat for MDS from the 2025 ASH Annual Meeting.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258306","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":"Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.","authors":"Jee-Eun Hwang, Jiwoo Park, Hong-Sik Kim, Shengjun Li, Hyung-Jun Im","doi":"10.1186/s13045-026-01811-9","DOIUrl":"10.1186/s13045-026-01811-9","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a structurally and functionally heterogeneous ecosystem in which extracellular matrix (ECM) remodeling, vascular-lymphatic dysfunction, hypoxia, acidosis, and spatially organized immunosuppressive networks jointly constrain nanoparticle accessibility, intratumoral distribution, and therapeutic efficacy. Conventional nanomedicine strategies based on passive accumulation, ligand-mediated targeting, and stimulus-responsive release have produced important advances, but they remain limited by empirical design principles that often overlook interpatient and intratumoral heterogeneity. Recent advances in single-cell profiling, spatial transcriptomics (ST), and complementary multi-omics technologies have revealed that the TME comprises regionally distinct stromal architectures, endothelial states, metabolic niches, proteolytic landscapes, and immune-stromal interaction networks. These datasets provide an opportunity to move beyond tumor-averaged descriptors by identifying cell-type-specific receptors, stromal and vascular barriers, spatially restricted release cues, and immune-excluded niches that govern nanoparticle transport, activation, and therapeutic response. In this review, we first summarize key TME barriers relevant to nanomedicine delivery, including ECM architecture, vascular pathophysiology, hypoxia, acidosis, and tumor immune microenvironment (TIME) dynamics. We then propose a closed-loop omics-to-design framework that translates spatially resolved biological features into actionable nanoparticle engineering parameters, including ligand selection, stromal-penetrating and barrier-modulating architectures, subtype-informed vascular delivery, and omics-defined responsive release strategies. Finally, we discuss the translational requirements for implementing this paradigm, including patient stratification, companion diagnostic development, chemistry, manufacturing, and controls (CMC) considerations, regulatory pathways, and the practical shift from fully personalized formulations toward stratification-matched libraries of pre-validated nanomedicines. By combining TME biology, spatial multi-omics, functional engineering, and translational planning, this review outlines an integrated strategy for next-generation precision nanomedicine designed to overcome tumor heterogeneity and enhance therapeutic efficacy.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217816","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":"Novel BTK inhibitors and degraders for relapsed/refractory CLL/SLL: latest updates from ASH 2025 annual meeting.","authors":"Pritika Sharma, Heng Jiang, Delong Liu","doi":"10.1186/s13045-026-01810-w","DOIUrl":"10.1186/s13045-026-01810-w","url":null,"abstract":"<p><p>Although covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have extended clinical benefit to relapsed/refractory (R/R) and BTKi-resistant chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), there remains an unmet need for additional B-cell receptor (BCR) pathway targeted therapies for highly refractory disease. This summary highlighted latest updates from the American Society of Hematology 2025 Annual Meeting on emerging BTK-directed agents in CLL/SLL, including next-generation non-covalent BTKi, dual-kinase inhibitors, and BTK degraders. Phase 1 studies of docirbrutinib and rocbrutinib demonstrated target engagement across wild-type and resistance-associated BTK mutations with encouraging safety profiles and preliminary efficacy signals in heavily pretreated populations. Birletinib, a dual LYN/BTK inhibitor, showed a high objective response rate in patients with prior exposure to BTKi, BCL-2 inhibitors, and BTK degraders. BTK degraders, including bexobrutideg and BGB-16673, demonstrated rapid and deep responses, activity in high-risk molecular subgroups, and manageable toxicity profiles, with recommended phase 2 doses established. Collectively, these latest updates support continued clinical development of novel agents to address resistance and disease progression in R/R CLL/SLL.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198973","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":"Circulating tumor DNA in breast cancer: updates from SABCS 2025.","authors":"Iris Zhi, Xianghui Zou, Min Sun, Nancy Chan, Naomi Ko, Neil Vasan, Shridar Ganesan, Cynthia Ma","doi":"10.1186/s13045-026-01808-4","DOIUrl":"10.1186/s13045-026-01808-4","url":null,"abstract":"<p><p>Circulating tumor DNA (ctDNA) has emerged as a transformative biomarker in breast cancer, enabling sensitive assessment of tumor burden, molecular residual disease, and treatment resistance. Data presented at the 2025 San Antonio Breast Cancer Symposium (SABCS) demonstrate that ctDNA has moved beyond prognostication to guide treatment in advanced hormone receptor positive disease, most notably in the phase III SERENA-6 trial, where ctDNA-detected ESR1 mutations prospectively triggered endocrine therapy switch and significantly improved clinical outcomes. In early-stage breast cancer, converging evidence across subtypes shows that ctDNA-defined minimal residual disease (MRD) robustly identifies patients at high risk of recurrence. Collectively, these findings position ctDNA as a potential biomarker for dynamic treatment adaptation, supporting the next phase of precision oncology focused on MRD-guided escalation, de-escalation, and therapeutic interception across the breast cancer continuum.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13220570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054980","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}