Journal of Hematology & Oncology最新文献

{"title":"Efficacy and safety of hetrombopag, a novel thrombopoietin receptor agonist, in children and adolescents with immune thrombocytopenia: results from a randomized, multicenter, placebo-controlled phase 3 trial.","authors":"Runhui Wu, Ju Gao, Yufeng Liu, Jie Yu, Shaoyan Hu, Hui Liang, Hui Jiang, Xiaowen Zhai, Min Zhou, Wenge Hao, Heng Mei, Fei Li, Yumei Chen, Wei Liu, Mei Yan, Runzi Li, Junye Xiong, Zhenyi Zhu, Xiaoling Cheng, Tianyou Wang","doi":"10.1186/s13045-026-01790-x","DOIUrl":"10.1186/s13045-026-01790-x","url":null,"abstract":"<p><strong>Background: </strong>Primary immune thrombocytopenia (ITP) is the most common acquired bleeding disorder in children, and management is challenging when first-line therapy fails. Hetrombopag is an oral thrombopoietin receptor agonist (TPO-RA). This phase 3 randomized, double-blind, placebo-controlled trial evaluated its efficacy and safety in children and adolescents with ITP who had an inadequate response or relapse after prior treatment.</p><p><strong>Methods: </strong>Children and adolescents aged 6-17 years were randomized 2:1 to receive once-daily hetrombopag (initial dose 2.5 mg) or placebo for 12 weeks, followed by a 12-week open-label hetrombopag extension. The primary endpoint was the proportion of patients with a platelet count ≥50 × 10⁹/L at Week 10. The key secondary endpoint was the proportion of patients with a sustained platelet response, defined as a platelet count ≥50 × 10⁹/L maintained for ≥6 weeks without rescue therapy between Weeks 5 and 12.</p><p><strong>Results: </strong>Eighty-eight patients were randomized (hetrombopag, n=57; placebo, n=31). At Week 10, 61.4% of patients in the hetrombopag group achieved the primary endpoint versus 9.7% in the placebo group (absolute difference, 52.7 percentage points; 95% CI, 35.9-69.5; P<0.0001). Sustained response was achieved in 43.9% of hetrombopag-treated patients and 0% of placebo-treated patients (absolute difference, 43.7 percentage points; 95% CI, 28.5-58.9; P<0.0001). Hetrombopag also reduced the need for rescue therapy (21.1% vs 45.2% during double-blind treatment). During the double-blind period, the most common adverse events with hetrombopag were upper respiratory tract infection (57.9% vs 45.2% with placebo) and epistaxis (19.3% vs 22.6%). Alanine aminotransferase elevations occurred in 7.0% of patients on hetrombopag and 0% on placebo. Over 24 weeks, treatment-related hepatotoxicity events (liver enzyme elevations or hepatic function abnormalities) occurred in 17.5% (10/57) of patients receiving continuous hetrombopag; all were grade 1-2 and none led to treatment discontinuation.</p><p><strong>Conclusions: </strong>Once-daily hetrombopag improved platelet responses, reduced rescue therapy use, and provided durable platelet control with an acceptable safety profile in children and adolescents with ITP. These findings support hetrombopag as an additional oral TPO-RA option for patients with inadequate response or relapse after first-line therapy.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifier: NCT04737850.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638971","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":"Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.","authors":"Shenghong Wu,Ran Cui,Kangnan Zhao,Zhen Yang,Zihan Yi,Weiwei Cao,Li Ye","doi":"10.1186/s13045-026-01795-6","DOIUrl":"https://doi.org/10.1186/s13045-026-01795-6","url":null,"abstract":"Gastrointestinal (GI) cancers account for nearly one-third of cancer-related deaths worldwide and often remain difficult to treat because of pronounced molecular heterogeneity and strongly immunosuppressive tumor microenvironments (TMEs). Antibody-drug conjugates (ADCs) deliver highly potent cytotoxic payloads to antigen-positive cells and may partially address intratumoral heterogeneity through bystander killing. In contrast, immunofusion proteins (IFPs)-including cytokine-antibody fusions and T-cell-redirecting modalities such as bispecific T-cell engagers-are designed to localize immune activation and/or retarget immune effectors within immunologically \"cold\", stroma-rich tumors. In this review, we integrate recent clinical and translational advances in ADCs and emerging IFP platforms across gastric, colorectal, pancreatobiliary and hepatocellular cancers, with particular attention to organ-dependent efficacy-toxicity trade-offs (e.g., interstitial lung disease (ILD) associated with DXd-based ADCs; cytokine release syndrome with T-cell engagers) and convergent resistance mechanisms, including antigen loss, impaired payload processing, immune exhaustion, and stromal exclusion. We further propose \"immunocytotoxic convergence\" as a hypothesis-generating and testable working model: under specific conditions, ADC-driven cytoreduction, immunogenic stress signatures consistent with immunogenic cell death (ICD), and/or stromal remodeling may transiently improve immune accessibility and thereby create a window for subsequent immune amplification by IFPs. Direct clinical evidence for an explicit ADC→IFP Prime-Amplify sequence in GI cancers remains limited. We therefore summarize the current evidence base, define key failure modes and safety constraints, and outline biomarker-enabled experimental and early-phase trial approaches needed to validate-or falsify-this sequencing concept.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"116 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147630179","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":"Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.","authors":"Ava Safaroghli-Azar,Laychiluh B Mekonnen,Jimma Lenjisa,Robert Milne,Shudong Wang","doi":"10.1186/s13045-026-01794-7","DOIUrl":"https://doi.org/10.1186/s13045-026-01794-7","url":null,"abstract":"Cyclin-dependent kinase (CDK) 4/6 inhibitors have reshaped the therapeutic landscape for hormone receptor (HR)-positive breast cancer and firmly established cell-cycle regulation as a viable target in oncology. Yet, despite strong biological rationale, their clinical impact outside this setting has expanded more slowly than anticipated. This review dissects key gaps in our understanding of CDK4/6-cyclin D signalling and its context-dependent roles in tumourigenesis. We begin by the outlining molecular biology of CDK4, CDK6, and D-type cyclins, highlighting their contributions to malignant proliferation and lineage-specific vulnerabilities. We then examine the therapeutic landscape defined by CDK4/6 inhibition, summarising key clinical successes as well as ongoing limitations, including resistance, restricted therapeutic applicability, and haematologic toxicities. Finally, we discuss emerging strategies to overcome these challenges, with particular emphasis on the development of next-generation, highly selective CDK4 inhibitors that may refine and extend the clinical utility of cell-cycle-targeted therapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"30 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625816","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":"CXCR4-antagonistic peptide-decorated lipid nanoparticles for co- delivery of AML1-ETO siRNA to enhance chemotherapy in refractory AML.","authors":"Xuelu Peng,Runxia Gu,Tao Wang,Chuanmei Jiang,Haiyan Xing,Jie Meng,Tao Wen,Jian Liu,Jianxiang Wang,Haiyan Xu","doi":"10.1186/s13045-026-01785-8","DOIUrl":"https://doi.org/10.1186/s13045-026-01785-8","url":null,"abstract":"Fusion protein AML1-ETO and chemokine receptor CXCR4 are crucial therapeutic targets for AML, the former plays a key role in differentiation blockade and leukemogenesis, and the latter is closely associated with drug resistance and relapse. This work developed a unified platform (referred as to E5-LNP@siAE) to integrate AML1-ETO-targeted RNA interference (RNAi) and CXCR4 antagonism by employing lipid nanoparticle (LNP) technology and antagonistic peptide E5 modification. The E5-LNP@siNC was slightly negative charged with 121.8 nm in diameter, showing homogenous spherical morphology and stability in PBS and 10% FBS. The E5-LNP@siAE could be specifically taken up by Kasumi-1 cells, down regulated levels of AML1-ETO, p-Erk and p-p38, and E5-LNP@siNC inhibited the CXCL12-mediated migration. In a refractory AML mouse model, E5-LNP@siAE monotherapy significantly reduced AML cells in peripheral blood, as well as infiltrations in the liver, lung and spleen. The expressions of CD11b, CD41a and Ter119 were upregulated while c-Kit decreased in the spleen of AML mice received E5-LNP@siAE treatment. The differentiation inductive effects were also observed in bone marrow mononuclear cells separated from AML patients with t(8;21) translocation. Moreover, E5-LNP@siAE significantly enhanced the therapeutic efficacy of doxorubicin (DOX) in the AML mice, evidenced by the reduced AML cells in peripheral blood, bone marrow and multiple organs, meanwhile, did not bring negative impacts on the counts of red blood cells and platelets. Consequently, the combination regimen achieved the much better result of survival prolongation than E5-LNP@siAE monotherapy, and the other control groups did not show therapeutic effects on the survival of the AML mice.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"89 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583999","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":"UVI5008: the first reversible, non-covalent Bruton's tyrosine kinase epi-inhibitor for B-cell malignancies.","authors":"Carmela Dell'Aversana, G Sgueglia, C Massaro, U Perricone, F Sarno, W L Megchelenbrink, M Conte, V Carafa, A Campanella, M Frenquelli, J Bordini, P Ghia, V B Petrizzi, R Alvarez, D Nappi, F Chiurazzi, F P Tambaro, W G Wierda, A R de Lera, Lucia Altucci","doi":"10.1186/s13045-026-01784-9","DOIUrl":"10.1186/s13045-026-01784-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic lymphocytic leukemia (CLL) can still be a therapeutic challenge; notwithstanding substantial progress in therapeutic approaches with small molecule inhibitors, the emergence of inhibitor resistance and suboptimal long-term outcomes highlight the persistent need for novel, more effective treatment strategies, especially targeting resistance.</p><p><strong>Patients and methods: </strong>Kinase activity screening was performed on UVI5008, followed by computational study. The findings were validated through a comprehensive set of in vitro and ex vivo assays, including enzymatic, cellular, transcriptional, genetic, epigenetic, and genomic assays, on primary CLL patient-derived peripheral blood mononuclear cells and cell lines, as well as through in vivo studies using genetically engineered mouse models.</p><p><strong>Results: </strong>We identified a novel tyrosine kinase inhibitory activity of UVI5008, currently the only known epigenetic modulator (epi-inhibitor) that directly targets Bruton's tyrosine kinase (BTK), affecting both BTK expression and enzymatic function. Our comprehensive analysis, combining in silico, ex vivo, and in vivo approaches, revealed that UVI5008 effectively inhibits both wild-type BTK and the C481S mutated BTK isoform, commonly associated with BTK-inhibitor resistance in CLL. Treatment with UVI5008 in B-cell lymphoma and leukemia disorders led to a substantial increase in cellular apoptosis, accompanied by a notable reduction in phosphorylation and BTK protein levels, as well as attenuation of downstream signaling, thus demonstrating superior efficacy compared to ibrutinib. Ex vivo treatment of patient-derived CLL samples and in vivo murine models corroborated these results, further supporting the potential of UVI5008 as a promising therapeutic agent.</p><p><strong>Conclusion: </strong>UVI5008 represents a promising pharmacological alternative to current BTK inhibitors. As the first-in-class, non-covalent, reversible, BTK inhibitor and epi-inhibitor of expression. UV15008 demonstrates potent in vitro anti-tumor efficacy in relapsed/refractory CLL cells, including cases with the C481S BTK mutation and in in vivo animal studies.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271199","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":"Allogeneic stem cell transplantation for major T-cell lymphoma entities: an analysis of the EBMT-lymphoma working party.","authors":"Evgenii Shumilov, Maud Ngoya, Philipp Berning, Raynier Devillier, Edouard Forcade, Thomas Schroeder, Frank Kroschinsky, Matthias Stelljes, Veronika Valkova, Francesca Kinsella, Patrice Chevallier, Gitte Olesen, Mohamad Mohty, Flore Sicre de Fontbrune, Eva Wagner-Drouet, Robert Zeiser, Marco Herling, Georg-Nikolaus Franke, Lucía López-Corral, Francis Ayuk, Georg Lenz, Gerald Wulf, Anna Sureda, Arain Laurence, Peter Dreger, Ali Bazarbachi, Norbert Schmitz","doi":"10.1186/s13045-026-01783-w","DOIUrl":"10.1186/s13045-026-01783-w","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic hematopoietic stem cell transplantation (allo-SCT) is an established treatment for peripheral T-cell lymphoma (PTCL), particularly for patients with relapsed/refractory (r/r) disease. We aimed to retrieve novel information on the role of histology, disease status prior to transplantation, and donor choice for patients with PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase (ALK)-negative ALCL. We compared imaging by computed tomography (CT) or positron emission tomography (PET) for defining disease status prior to allo-SCT.</p><p><strong>Methods: </strong>Eligible were adult patients with PTCL-NOS, AITL, and ALK-negative ALCL undergoing allo-SCT between 2010 and 2022 and reported to EBMT.</p><p><strong>Results: </strong>1958 patients underwent allo-SCT. Of patients with known number of prior lines of therapies (n = 1310), 301 (23%), 431 (32.9%) and 578 (44.1%) patients received allo-SCT after one (1L), two (2L) or three or more therapy lines (3L +), respective. Three-year GvHD-free, relapse-free survival (GRFS), progression-free survival (PFS) and overall survival (OS) were 35.8%, 50.9% and 56.8%, respectively. Three-year relapse incidence (RI) and non-relapse mortality were 25.1% and 24.1%, respectively. In multivariate analysis, histology other than AITL, no complete response (CR) at transplantation, having a haploidentical donor and higher age at allo-SCT resulted in significantly lower PFS and/or OS. Prior autologous SCT had no impact on the results of allo-SCT and major outcomes did not significantly change when the analyses were restricted to the patients with PET-based response at allo-SCT. Patients allografted in partial response (PR) or SD/PD still achieved long-term survival with a 3-year PFS/OS of 46%/53.7% and 39.6%/43.6%, respectively.</p><p><strong>Conclusion: </strong>Allo-SCT is a valid treatment option in relapsed/refractory PTCL where targeted therapies still play a limited role. Patients with AITL survived significantly better than patients with PTCL NOS or ALK-negative ALCL following a significantly lower RI, also when comparing CR/complete metabolic response (CMR) and PR patients separately. Higher age and non-CR at allo-SCT are associated with worse outcomes.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12930567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776273","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":"IL-5 CAR-T cell therapy induces effective remission in hypereosinophilic disorders.","authors":"Youqian Wu, Ruiqi Zhang, Beibei Sun, Gaoying Chen, Fang Xu, Xinyi Chen, Jiayuan Zeng, Dan Shen, Fan Shi, Sheng Pan, Bingpeng Yao, Haoyu Tang, Zhehua Shao, Qian Wu, Jiawei Shao, Chao Zhang, Dongrui Wang, Yongxian Hu, Songmin Ying","doi":"10.1186/s13045-026-01782-x","DOIUrl":"10.1186/s13045-026-01782-x","url":null,"abstract":"<p><strong>Background: </strong>Clonal and pathogenic eosinophil expansion in hypereosinophilic disorders (e.g., refractory hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL)) remains an unmet therapeutic challenge, with current strategies often failing to induce durable remission. While monoclonal antibodies targeting the IL-5/IL-5Rα pathway have shown efficacy in treating eosinophil-driven diseases, a subset of patients experience incomplete responses or relapse, highlighting the need for more durable and comprehensive therapeutic strategies. Chimeric antigen receptor T (CAR-T) cell therapy, with its potential for long-term persistence and durable remission after a single infusion, represents a promising alternative for patients with refractory disease.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on peripheral blood (PB) and bone marrow (BM) samples from both healthy individuals and the patient with hypereosinophilic disorder, to identify key therapeutic targets for intervention. Based on these findings, we developed a first-in-class chimeric antigen receptor T-cell (CAR-T) therapy using human interleukin-5 (hIL-5) as a ligand-based targeting domain, to selectively recognize and eliminate IL-5Rα⁺ eosinophils and precursors. In vitro cytotoxicity assays and IFN-γ secretion were measured against target cells and patient-derived PB/BM samples. Preclinical safety was assessed through comprehensive toxicity assessment. Efficacy was evaluated in a hypereosinophilic leukemia mouse model, with tumor burden reduction and survival as the key evaluation indicators.</p><p><strong>Results: </strong>Single-cell profiling revealed concurrent expansion of both eosinophil progenitors and mature eosinophils in the BM and PB, highlighting the need for therapies targeting all stages of eosinophil development. IL-5 receptor α (IL-5Rα) was identified as the optimal target due to its high expression across all stages of eosinophil development, with relatively restricted expression on non-eosinophil immune populations. hIL-5 CAR-T cells demonstrated potent in vitro cytotoxicity and IFN-γ secretion against target cells and effectively eliminated eosinophils in patient-derived PB/BM samples. No dose-limiting toxicities were observed, and no evidence of cytokine release syndrome (CRS) was detected in preclinical models. In the hypereosinophilic leukemia mouse model, a single infusion of hIL-5 CAR-T cells significantly reduced tumor burden and extended survival, demonstrating its therapeutic potential.</p><p><strong>Conclusions: </strong>IL-5 CAR-T cell therapy represents a promising targeted therapeutic approach for IL-5Rα⁺ hypereosinophilic disorders. Its ability to target eosinophils and their precursors across all developmental stages in BM and PB addresses a critical unmet medical need in refractory HES and CEL.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194671","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":"The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.","authors":"Jiayi Li, Chen Huang, Pan Tang, Ruiyan Wu, Quanyou Wu, Chenliang Zhang","doi":"10.1186/s13045-026-01780-z","DOIUrl":"10.1186/s13045-026-01780-z","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) are crucial signaling molecules that regulate diverse biological processes. In cancer, this duality gives rise to a central paradox. Moderate ROS levels support tumor proliferation and foster an immunosuppressive microenvironment, whereas excessive ROS can be therapeutically leveraged to trigger immunogenic cell death (ICD). Crucially, the outcome on immune cells, whether activation or exhaustion, is dictated by the subcellular localization and kinetics of ROS generation. This review critically examines this \"ROS-Immune Mismatch,\" a new framework that highlights the differential redox sensitivities between tumor cells and key immune subsets. This differential sensitivity, where cytotoxic T cells (Teffs) are exhausted and immunosuppressive cells like regulatory T cells (Tregs) thrive, is a fundamental mechanism of immune evasion. We further analyze how emerging immunotherapies seek to exploit these redox dependencies to enhance therapeutic efficacy. Finally, we discuss major translational challenges, including off-target oxidative toxicity and redox heterogeneity within the tumor microenvironment (TME), and highlight future directions, such as intelligent nanomedicine and redox-reprogrammed cellular therapies, as promising strategies for next-generation ROS-targeted immunomodulation.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":"16"},"PeriodicalIF":47.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165284","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":"Implementing generative artificial intelligence in precision oncology: safety, governance, and significance.","authors":"Ryuji Hamamoto, Takafumi Koyama, Satoshi Takahashi, Tomohiro Yasuda, Kazuma Kobayashi, Yu Akagi, Nobuji Kouno, Kazuki Sudo, Makoto Hirata, Kuniko Sunami, Takashi Kubo, Hiroshi Katayama, Atsuo Takashima, Tomonori Taniguchi, Hiromi Matsumoto, Ryota Shibaki, Ken Asada, Masaaki Komatsu, Syuzo Kaneko, Masayoshi Yamada, Hidehito Horinouchi, Katsuya Tanaka, Yasushi Goto, Ken Kato, Yutaka Saito, Kenichi Nakamura, Noboru Yamamoto","doi":"10.1186/s13045-026-01781-y","DOIUrl":"10.1186/s13045-026-01781-y","url":null,"abstract":"<p><p>The paramount challenge in precision oncology lies in further improving quality of life and response rates for individual patients. Efforts toward these goals are steadily expanding the scope of clinical implementation, despite ongoing challenges such as standardization, cost-effectiveness, and data harmonization. Building upon this maturing foundation, generative AI-which has evolved dramatically in recent years-is particularly valuable at this stage of advancing efficiency and adoption as an auxiliary technology linking literature, guidelines, trial protocols, and patient data. Specifically, through mutation interpretation, trial eligibility matching, and tumor board support, it is expected to contribute to advancing standardization, improving cost-effectiveness, accelerating data harmonization, and further accelerating human-centered decision-making. Accordingly, this review surveys the development history of generative AI and its current healthcare applications, organizing its implementation potential for precision oncology along three axes: (1) generative AI-based interpretation of genetic mutations and estimation of their pathological significance; (2) generative AI-driven verification of clinical trial eligibility; and (3) multimodal foundation models for imaging and pathology that compute \"tumor phenotypes\" using real-world data, contributing to report drafting and molecular surrogate estimation. In response, we propose a strategy centered on retrieval-augmented generation (RAG) and human-in-the-loop (HITL) workflows, encompassing data preparation based on OMOP, mCODE, and FHIR; multicenter prospective evaluation; auditable logs and governance aligned with Good Manufacturing Practice (GMP) and the EU AI Act; and a synthetic data strategy including differential privacy. Ultimately, this approach validates value through real-world outcomes and charts a path toward \"learning oncology,\" accelerating patient-centered decision-making and clinical trial development.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":"14"},"PeriodicalIF":47.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149988","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":"Lung cancer vaccines to enhance immune checkpoint inhibitor therapy: evidence and future perspectives.","authors":"Zhiting Tang, Linjun Zha, Ruqiang Liang, Tianhong Li","doi":"10.1186/s13045-026-01778-7","DOIUrl":"10.1186/s13045-026-01778-7","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of lung cancer over the past decade, markedly improving antitumor responses, overall survival, and quality of life. However, durable clinical benefit is achieved in only a subset of patients, and resistance to ICIs remains a major clinical challenge. Mechanistically, resistance arises from multiple, often overlapping processes, including inadequate tumor antigen presentation, dysfunctional T-cell priming and expansion, and the presence of physical and immunosuppressive barriers within the tumor microenvironment that limit immune cell infiltration and effector function. Cancer vaccines have re-emerged as a rational immunotherapeutic strategy to overcome these obstacles by inducing de novo or amplifying pre-existing tumor-specific immune responses, thereby enhancing long-term immunological memory while maintaining a favorable safety profile. Advances in antigen discovery, neoantigen prediction, and vaccine platforms have accelerated the development of both personalized and off-the-shelf neoantigen vaccines. Although personalized neoantigen vaccines have gained considerable attention following the success of mRNA-based COVID-19 vaccines, off-the-shelf approaches offer advantages in scalability, cost, and manufacturing timelines, facilitating broader clinical implementation. Accumulating preclinical and clinical evidence suggests that cancer vaccines are more effective in the adjuvant setting than in the metastatic setting, where high tumor burden and an immunosuppressive tumor microenvironment constrain vaccine-induced immune responses. Consistent with their limited efficacy as monotherapy, contemporary clinical trials increasingly evaluate cancer vaccines in combination with ICIs or other immunotherapeutic agents to enhance T-cell activation, reverse immune suppression, and restore antitumor immunity. This review synthesizes current mechanistic insights, highlights ongoing clinical efforts, and discusses future directions for rational cancer vaccine development in lung cancer, with an emphasis on overcoming resistance to ICI.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":"15"},"PeriodicalIF":47.8,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113374","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}