Journal of Hematology & Oncology最新文献

{"title":"CD19 CAR-T in relapsed t(8;21) AML: a single-center prospective phase II clinical trial.","authors":"Jia Yin,Qing-Ya Cui,Hai-Ping Dai,Chang-Ju Qu,Zheng Li,Li-Qing Kang,Wei Cui,Xiao-Peng Tian,Xia-Ming Zhu,Lei Yu,De-Pei Wu,Xiao-Wen Tang","doi":"10.1186/s13045-025-01708-z","DOIUrl":"https://doi.org/10.1186/s13045-025-01708-z","url":null,"abstract":"Approximately 78.3% of patients with t(8;21) acute myeloid leukemia (AML) express CD19, making it a potential target for chimeric antigen receptor (CAR)-T cell therapy focused on CD19. This prospective phase II trial (NCT03896854) evaluated the safety and efficacy of CD19 CAR-T cell treatment in 10 relapsed CD19-positive t(8;21) AML patients. This study enrolled eight patients with hematologic and two with molecular relapsed AML. The median bone marrow blast percentage was 12.4% (0.1-50.2%), and the blasts exhibited a median CD19 positivity of 55.7% (22.6-97.1%). Genetic profiling revealed TP53 alterations (n = 1), KIT (n = 3) and FLT3-ITD (n = 1) mutations. After lymphodepletion with fludarabine and cyclophosphamide (FC), 5-20 × 106 cells per kilogram of CAR-T cells were administered. All patients experienced grade 3 or higher hematologic toxicities following tumor-reduction chemotherapy and the FC regimen, which were managed for a median of two weeks after CAR-T treatment. Non-hematological toxicities were mild and reversible. Eight patients presented with mild (grade 1-2) cytokine release syndrome (CRS), and one experienced grade 3 CRS. The immune effector cell-associated neurotoxicity syndrome was not observed. All patients achieved complete remission (CR) after CAR-T, with 60% achieving a molecularly MRD-negative CR. RUNX1::RUNX1T1 fusion transcript levels demonstrated a median 2.5-log reduction (range: 0.7-4.5 log; P = 0.002). At a median follow-up of 64.6 months (range: 11.2-88.8 months), the median overall survival and leukemia-free survival were 11.6 and 3.8 months, respectively. The 12-month cumulative incidence of relapse was 53.3%. These findings indicated that CD19 CAR-T was a safe and effective option for relapsed CD19-positive t(8;21) AML.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"16 1","pages":"53"},"PeriodicalIF":28.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915089","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":"Targeted degradation of extracellular proteins: state of the art and diversity of degrader designs","authors":"M. A. A. Mamun, Anush G. Bakunts, Alexander L. Chernorudskiy","doi":"10.1186/s13045-025-01703-4","DOIUrl":"https://doi.org/10.1186/s13045-025-01703-4","url":null,"abstract":"Selective elimination of proteins associated with the pathogenesis of diseases is an emerging therapeutic modality with distinct advantages over traditional inhibitor-based approaches. This strategy, called targeted protein degradation (TPD), is based on hijacking the cellular proteolytic machinery using chimeric degrader molecules that physically link the target protein of interest with the degradation effectors. The TPD era began with the development of PROteolysis TAtrgeting Chimeras (PROTACs) in 2001, with various methods and applications currently available. Classical PROTAC molecules are heterobifunctional chimeras linking target proteins with E3 ubiquitin ligases. This induced interaction leads to the ubiquitylation of the target protein, which is needed for its recognition and subsequent degradation by the cellular proteasomes. However, this technology is limited to intracellular proteins since the effectors involved (E3 ubiquitin ligases and proteasomes) are located in the cytosol. The related methods for selective destruction of proteins present in the extracellular space have only emerged recently and are collectively termed extracellular TPD (eTPD). The prototypic eTPD technology utilizes LYsosomal TArgeting Chimeras (LYTACs) that link extracellular target proteins (secreted or membrane-associated) to lysosome-targeting receptors (LTRs) on the cell surface. The resulting complex is then internalized by endocytosis and trafficked to lysosomes, where the target protein is degraded. The successful elimination of various extracellular proteins via LYTACs and related approaches has been reported, including several important targets in oncology that drive tumor growth and dissemination. This review summarizes current progress in the eTPD field and focuses primarily on the respective technological developments. It discusses the design principles and diversity of degrader molecules and the landscape of available targets and effectors that can be employed for eTPD. Finally, it emphasizes current open questions, challenges, and perspectives of this technological platform to promote the expansion of the eTPD toolkit and further development of its therapeutic applications.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"72 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893130","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":"Antibody–Drug Conjugates (ADCs): current and future biopharmaceuticals","authors":"Ruili Wang, Baohui Hu, Ziyu Pan, Chongxia Mo, Xin Zhao, Guojia Liu, Ping Hou, Qi Cui, Zhao Xu, Wenjia Wang, Zhaojin Yu, Lin Zhao, Miao He, Yan Wang, Chen Fu, Minjie Wei, Lifeng Yu","doi":"10.1186/s13045-025-01704-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01704-3","url":null,"abstract":"Antibody–drug conjugates (ADCs) represent a novel class of biopharmaceuticals comprising monoclonal antibodies covalently conjugated to cytotoxic agents via engineered chemical linkers. This combination enables targeted delivery of cytotoxic agents to tumor site through recognizing target antigens by antibody while minimizing off-target effects on healthy tissues. Clinically, ADCs overcome the limitations of traditional chemotherapy, which lacks target specificity, and enhance the therapeutic efficacy of monoclonal antibodies, providing higher efficacy and fewer toxicity anti-tumor biopharmaceuticals. ADCs have ushered in a new era of targeted cancer therapy, with 15 drugs currently approved for clinical use. Additionally, ADCs are being investigated as potential therapeutic candidates for autoimmune diseases, persistent bacterial infections, and other challenging indications. Despite their therapeutic benefits, the development and application of ADCs face significant challenges, including antibody immunogenicity, linker instability, and inadequate control over the release of cytotoxic agent. How can ADCs be designed to be safer and more efficient? What is the future development direction of ADCs? This review provides a comprehensive overview of ADCs, summarizing the structural and functional characteristics of the three core components, antibody, linker, and payload. Furthermore, we systematically assess the advancements and challenges associated with the 15 approved ADCs in cancer therapy, while also exploring the future directions and ongoing challenges. We hope that this work will provide valuable insights into the design and optimization of next-generation ADCs for wider clinical applications.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"34 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893133","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":"A multicenter, open-label, single-arm, phase Ib clinical trial of HH2853 treatment in patients with relapsed and/or refractory peripheral T-cell lymphoma","authors":"Huangming Hong, Zegeng Chen, Mingzhi Zhang, Zhigang Peng, Jianzhen Shen, Yuerong Shuang, Hui Zhou, Hongqiang Guo, He Huang, Fei Li, Zhengzi Qian, Lihong Liu, Liang Wang, Wei Yang, Liling Zhang, Pengcheng He, Shen Qian, Fugen Li, Meng Li, Tongyu Lin","doi":"10.1186/s13045-025-01697-z","DOIUrl":"https://doi.org/10.1186/s13045-025-01697-z","url":null,"abstract":"Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL. A phase Ib clinical trial in PTCL was conducted from July 2022–August 2023 at 15 sites in China. The study employed a dose-escalation phase (300 mg, 400 mg, and 600 mg BID) to determine the recommended phase II dosage (RP2D), followed by a dose expansion phase (300 mg and 400 mg BID). The primary endpoints were safety and the overall response rate (ORR). Thirty-four patients with various r/r PTCL histology types, a median age of 58 years, and a median of 2 prior systemic therapies were enrolled. Treatment-related adverse events (TRAEs) were observed in 92.1% of the patients, with 20.6% experiencing grade 3 TRAEs. The most common TRAEs included anemia (67.6%), thrombocytopenia (52.9%), leukopenia (44.1%), and diarrhea (38.2%). One patient (2.9%) receiving 600 mg BID experienced dose-limiting toxicity due to grade 4 thrombocytopenia. The dose of 400 mg BID was selected as the RP2D. The ORR was 67.6%, comprising 29.4% complete remission and 38.2% partial remission. As of the data cutoff in September 2024, the median follow-up period was 15.7 months, with a median duration of response of 14.8 months; overall survival had not yet been reached. The selective EZH1/2 dual inhibitor HH2853 demonstrated acceptable and manageable safety profiles and promising efficacy in r/r PTCL patients, indicating its therapeutic potential for this difficult-to-treat patient population. NCT04390737","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878128","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":"Correction: The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications","authors":"Mengzhou Shen, Xianjie Jiang, Qiu Peng, Linda Oyang, Zongyao Ren, Jiewen Wang, Mingjing Peng, Yujuan Zhou, Xiyun Deng, Qianjin Liao","doi":"10.1186/s13045-025-01706-1","DOIUrl":"https://doi.org/10.1186/s13045-025-01706-1","url":null,"abstract":"<p><b>Correction: Journal of Hematology & Oncology (2025) 18:40</b></p><p><b>https://doi.org/10.1186/s13045-025-01691-5</b></p><p>The original article has been updated to restore Qianjin Liao to Corresponding Authorship.</p><span>Author notes</span><ol><li><p>Mengzhou Shen and Xianjie Jiang contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Department of Oncology, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal University, Hunan Normal University Health Science Center, Changsha, Hunan, 410005, China</p><p>Mengzhou Shen, Jiewen Wang & Qianjin Liao</p></li><li><p>The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Key Laboratory of Cancer Metabolism, Central South University, Hunan Cancer Hospital, Changsha, Hunan, 410013, China</p><p>Mengzhou Shen, Xianjie Jiang, Qiu Peng, Linda Oyang, Zongyao Ren, Jiewen Wang, Mingjing Peng & Yujuan Zhou</p></li><li><p>School of Basic Medical Sciences, Hunan Normal University, Changsha, Hunan, 410013, China</p><p>Xiyun Deng</p></li><li><p>Hunan Engineering Research Center of Tumor Organoid Technology and Application, Public Service Platform of Tumor Organoids Technology, Changsha, Hunan, 410013, China</p><p>Yujuan Zhou & Qianjin Liao</p></li></ol><span>Authors</span><ol><li><span>Mengzhou Shen</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xianjie Jiang</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Qiu Peng</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Linda Oyang</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Zongyao Ren</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Jiewen Wang</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Mingjing Peng</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yujuan Zhou</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xiyun Deng</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Qianjin Liao</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Corresponding authors</h3><p>Corresp","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878127","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":"PFS24 as a prognostic milestone in patients with newly diagnosed primary CNS lymphoma","authors":"Vanja Zeremski, Tobias R. Haage, Hanno M. Witte, Louisa Adolph, Sina A. Beer, Gerhard Behre, Benedikt Jacobs, Christoph Kahl, Chrysavgi Lalayanni, Jens Panse, Sotirios Papageorgiou, Marina P. Siakantaris, Jessica Schneider, Ulf Schnetzke, Alexander Schulz, Theodoros P. Vassilakopoulos, Jeanette Walter, Dimitrios Mougiakakos","doi":"10.1186/s13045-025-01700-7","DOIUrl":"https://doi.org/10.1186/s13045-025-01700-7","url":null,"abstract":"High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has significantly improved overall survival (OS) in primary central nervous system lymphoma (PCNSL). However, early identification of long-term survivors remains a challenge. Progression-free survival at 24 months (PFS24) has emerged as a key prognostic marker in diffuse large B-cell lymphoma, but its relevance in PCNSL is still unclear. In this retrospective multicenter study, we analyzed data from 146 newly diagnosed, transplant-eligible PCNSL patients treated with MATRix-like regimens across 14 hospitals. With a median follow-up of 48 months, the 2-year PFS and OS rates were 50.4% and 65.6%, respectively. Of the 139 patients evaluable for PFS24-analysis, 51.1% reached PFS24, with a subsequent 5-year OS of 96.7%. Of note, the annual hazard rate for progression and death decreased to under 5% after 24 months, remaining stable thereafter. The patients who failed to reach PFS24 had a median OS of only 6.0 months. Key predictors of PFS failure included impaired Karnofsky performance status and treatment dose-reduction. In conclusion, PFS24 was identified as an important prognostic marker in PCNSL. Patients who achieve PFS24 have a favorable prognosis, whereas those who do not face poor outcomes and require innovative treatment approaches. This insight could aid in risk stratification and support the use of PFS24 as a surrogate endpoint in clinical trials.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873036","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":"CD20 xCD3 bispecific antibodies for large B cell lymphoma: latest updates from 2024 ASH annual meeting","authors":"V. Tomarchio, L. Rigacci, O. Annibali","doi":"10.1186/s13045-025-01695-1","DOIUrl":"https://doi.org/10.1186/s13045-025-01695-1","url":null,"abstract":"Bispecific antibodies (BsAbs) represent an innovative class of off-the-shelf T-cell redirecting agents and are considered among the most promising immunotherapeutic strategies for the treatment of lymphoma. Notably, anti-CD20 × CD3 BsAbs have exhibited substantial monotherapy efficacy in patients with heavily pretreated B-cell non-Hodgkin lymphoma (B-NHL), showing a tolerable toxicity profile predominantly associated with T-cell activation-related side effects. In this study, we summarized several latest reports on CD20 × CD3 bsAbs for the therapy of Large B Cell Lymphoma (LBCL), also in first line, from the ASH 2024 annual meeting (ASH 2024).","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"71 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862739","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":"Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease","authors":"Vanessa Desantis, Alessandro Andriano, Tim Düking, Olga Hartwig, Giuseppe Ingravallo, Marta Biondo, Cirino Botta, Roberto Ria, Angelo Vacca, Antonio Giovanni Solimando","doi":"10.1186/s13045-025-01699-x","DOIUrl":"https://doi.org/10.1186/s13045-025-01699-x","url":null,"abstract":"Extramedullary disease (EMD) in multiple myeloma (MM) represents a significant clinical challenge, with a limited understanding of the spatial architecture and its pathobiological impact. To address this unmet need, we examined 10 matched samples from bone marrow (BM) and cognate EMD sites. This investigation provides critical insights into the distinct features of EMD, offering potential avenues for more effective diagnosis and targeted therapies. To this aim, we employed MACSima™ Imaging Cyclic Staining (MICS) to unveil distinct biomarker expression profiles as companion diagnostics for a personalized therapeutic approach for MM. We observed elevated BCL-2 levels in EMD plasma cells (p < 0.0001), indicating the potential of BCL-2 inhibitors to target anti-apoptotic pathways in select cases. The higher expression of EZH2 in EMD compared to BM (p < 0.0001) highlights its role in sustaining aggressive tumor phenotypes and supports the use of epigenetic-targeting agents in key situations. In contrast, CD3 + T-cell distance was significantly higher in EMD, reflecting impaired immune surveillance (p < 0.0001). Across the cohort, our analysis revealed significant differences between BM and EMD regarding the expression and spatial organization of key markers. CD38 expression was markedly reduced in EMD plasma cells (p < 0.0001). These findings underscore profound biological heterogeneity in MM and its BM emancipated disease phenotype, emphasizing dysfunctional apoptosis, immune evasion and resistance to CD38-targeting therapies in EMD, conceivably informing future validations. By integrating high-dimensional data, this study provides insights into potential druggable vulnerabilities for crafted interventions, particularly challenging in EMD cases.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866639","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":"Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer","authors":"Lirui Tang, Haiying Que, Yuquan Wei, Ting Yang, Aiping Tong, Xiawei Wei","doi":"10.1186/s13045-025-01694-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01694-2","url":null,"abstract":"Replicon RNA (RepRNA) represents a cutting-edge technology in the field of vaccinology, fundamentally transforming vaccine design and development. This innovative approach facilitates the induction of robust immune responses against a range of infectious diseases and cancers. RepRNA vaccines leverage the inherent capabilities of RNA-dependent RNA polymerase associated with self-replicating repRNA, allowing for extreme replication within host cells. This process enhances antigen production and subsequently stimulates adaptive immunity. Additionally, the generation of double-stranded RNA during RNA replication can activate innate immune responses. Numerous studies have demonstrated that repRNA vaccines elicit potent humoral and cellular immune responses that are broader and more durable than those generated by conventional mRNA vaccines. These significant immune responses have been shown to provide protection in various models for infectious diseases and cancers. This article will explore the design and delivery of RepRNA vaccines, the mechanisms of immune activation, preclinical studies addressing infectious diseases and tumors, and related clinical trials that focus on safety and immunogenicity.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841346","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":"KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma","authors":"Mahmoud Yousef, Abdelrahman Yousef, Mark W. Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L. Lewis, Paul M. Roy, Mohammad Fanaeian, Sali Albarouki, Luca F. Castelnovo, Jennifer Peterson, Brandon G. Smaglo, Robert A. Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P. Kim, Naruhiko Ikoma, Jess E. Maxwell, Matthew H. G. Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B. Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao","doi":"10.1186/s13045-025-01696-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01696-0","url":null,"abstract":"The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7–4.3, P < 0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"60 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841343","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}