Journal of Hematology & Oncology最新文献

{"title":"Correction: Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation","authors":"Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber","doi":"10.1186/s13045-025-01662-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01662-w","url":null,"abstract":"<p><b>Correction: Journal of Hematology & Oncology (2024) 17:104</b> <b>https://doi.org/10.1186/s13045-024-01622-w</b></p><p>The authors wish to note the following amendments to the affiliations and the funding in the original article.</p><br/><p>The affiliations should instead be as follows:</p><p>• Wael Saber:</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><p>• Paul Auer:</p><br/><p>Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><br/><p>Cancer Center Biostatistics Shared Resource, Medical College of Wisconsin, Milwaukee, WI</p><p>• Zhongyuan Chen:</p><br/><p>Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><br/><p>The Funding should instead read as follows:</p><p>Jing Dong is supported by the NHLBI (K01 HL164972) and the Medical College of Wisconsin Cancer Center. N00014-17-1-2850 from the Office of Naval Research. CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); and N00014-23-1-2057 and N00014-24-1-2057 from the Office of Naval Research. Support is also provided by the Medical College of Wisconsin, NMDP, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Elevance Health; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Medac GmbH; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biotec, Inc.; MorphoSys; MSA-EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, In","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"61 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077453","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":"N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential","authors":"Qihui Wu, Xiaodan Fu, Guoqian Liu, Xiaoyun He, Yimin Li, Chunlin Ou","doi":"10.1186/s13045-025-01665-7","DOIUrl":"https://doi.org/10.1186/s13045-025-01665-7","url":null,"abstract":"N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression. On one hand, m7G modification-associated modulate tumour progression and affect malignant biological characteristics, including sustained proliferation signalling, resistance to cell death, activation of invasion and metastasis, reprogramming of energy metabolism, genome instability, and immune evasion. This suggests that they may be novel therapeutic targets for cancer treatment. On the other hand, the aberrant expression of m7G modification-associated molecules is linked to clinicopathological characteristics, including tumour staging, lymph node metastasis, and unfavourable prognoses in patients with cancer, indicating their potential as tumour biomarkers. This review consolidates the discovery, identification, detection methodologies, and functional roles of m7G modification, analysing the mechanisms by which m7G modification-associated molecules contribute to tumour development, and exploring their potential clinical applications in cancer diagnostics and therapy, thereby providing innovative strategies for tumour identification and targeted treatment.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"84 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054936","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: Bortezomib-releasing silica-collagen xerogels for local treatment of osteolytic bone- and minimal residual disease in multiple myeloma","authors":"Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Reinhard Schnettler, Kim de Veirman, Thaqif El Khassawna, Christian Heiss, Anne Hild, Daniel Zahner, Francisca Alagboso, Anja Henss, Susanne Beck, Martina Emde-Rajaratnam, Jürgen Burhenne, Juliane Bamberger, Eline Menu, Elke de Bruyne, Michael Gelinsky, Marian Kampschulte, Marcus Rohnke, Sabine Wenisch, Karin Vanderkerken, Thomas Hanke, Anja Seckinger, Volker Alt","doi":"10.1186/s13045-025-01663-9","DOIUrl":"https://doi.org/10.1186/s13045-025-01663-9","url":null,"abstract":"<p><b>Journal of Hematology & Oncology (2024) 17:128</b></p><p><b>https://doi.org/10.1186/s13045-024-01636-4</b></p><p>The original article mistakenly omitted last author, Volker Alt as a co-Corresponding Author due to an error mistakenly carried forward by the production team.</p><p>Dr. Alt has since been restored as co-Corresponding Author.</p><span>Author notes</span><ol><li><p>Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Thomas Hanke, Anja Seckinger and Volker Alt have contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Laboratory of Hematology and Immunology & Labor für Myelomforschung, Vrije Universiteit Brussel, Laarbeeklaan 103, Jette, 1090, Belgium</p><p>Dirk Hose, Ulrich Thormann, Kim de Veirman, Susanne Beck, Martina Emde-Rajaratnam, Eline Menu, Elke de Bruyne, Karin Vanderkerken & Anja Seckinger</p></li><li><p>Experimentelle Unfallchirurgie (ForMED), Justus-Liebig-Universität Gießen, Aulweg 128, 35392, Gießen, Germany</p><p>Seemun Ray, Thaqif El Khassawna, Christian Heiss, Francisca Alagboso & Volker Alt</p></li><li><p>Institut für Werkstoffwissenschaft, Max-Bergmann-Zentrum für Biomaterialien, Technische Universität Dresden, Budapester Straße 27, 01069, Dresden, Germany</p><p>Sina Rößler & Thomas Hanke</p></li><li><p>Justus-Liebig-Universität Gießen, Ludwigstraße 23, 35392, Gießen, Germany</p><p>Reinhard Schnettler & Daniel Zahner</p></li><li><p>Klinische Anatomie und Experimentelle Chirurgie C/O Institut für Veterinär-Anatomie, -Histologie und - Embryologie, Justus-Liebig-Universität Gießen, Frankfurter Straße 98, 35392, Gießen, Germany</p><p>Anne Hild & Sabine Wenisch</p></li><li><p>I. Physikalisches Institut, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 16, 35392, Gießen, Germany</p><p>Anja Henss</p></li><li><p>Innere Medizin IX - Abteilung für Klinische Pharmakologie und Pharmakoepidemiologie, Medizinische Fakultät/Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany</p><p>Jürgen Burhenne</p></li><li><p>Labor Für Experimentelle Radiologie, Justus-Liebig-Universität Gießen, Carl-Maria-von-Weber-Straße 8, 35392, Gießen, Germany</p><p>Juliane Bamberger & Marian Kampschulte</p></li><li><p>Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany</p><p>Michael Gelinsky</p></li><li><p>Physikalisch-Chemisches Institut, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 17, 35392, Gießen, Germany</p><p>Marcus Rohnke</p></li><li><p>Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany</p><p>Volker Alt</p></li></ol><span>Authors</span><ol><li><span>Dirk Hose</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Seemun Ray</span>View author publications<p>You can also search f","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"13 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027224","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":"Helicobacter pylori and gastric cancer: mechanisms and new perspectives","authors":"Yantao Duan, Yonghu Xu, Yi Dou, Dazhi Xu","doi":"10.1186/s13045-024-01654-2","DOIUrl":"https://doi.org/10.1186/s13045-024-01654-2","url":null,"abstract":"Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world’s population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis—key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori’s role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020545","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":"WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome","authors":"Zwi N. Berneman, Maxime De Laere, Paul Germonpré, Manon T. Huizing, Yannick Willemen, Eva Lion, Hans De Reu, Jolien Van den Bossche, Jan Van den Brande, Pol Specenier, Sevilay Altintas, Peter A. van Dam, Nathalie Cools, Griet Nijs, Barbara Stein, Kim Caluwaerts, Annemiek Snoeckx, Bart Op de Beeck, Kirsten Saevels, Lynn Rutsaert, Irma Vandenbosch, Gizem Oner, Martin Lammens, Pierre Van Damme, Sian Llewellyn-Lacey, David A. Price, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama, Marie M. Couttenye, Ann L. Van de Velde, Viggo F. Van Tendeloo, Marc Peeters, Sébastien Anguille, Evelien L.J.M. Smits","doi":"10.1186/s13045-025-01661-x","DOIUrl":"https://doi.org/10.1186/s13045-025-01661-x","url":null,"abstract":"Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms’ tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"45 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020549","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":"Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects","authors":"Ada Alice Dona, Theophilus Tandoh, Lokesh Nigam, Mahmoud Singer, Enrico Caserta, Mariam Murtadha, Yinghui Zhu, Milad Moloudizargari, Preeti Sharma, Ottavio Napolitano, Janet Winchester, Arnab Chowdhury, Alex Pozhitkov, James F. Sanchez, Hawa Vahed, Guido Marcucci, Matt Coffey, Gerard Nuovo, Douglas W. Sborov, Flavia Pichiorri, Craig C Hofmeister","doi":"10.1186/s13045-024-01645-3","DOIUrl":"https://doi.org/10.1186/s13045-024-01645-3","url":null,"abstract":"Reovirus (RV) is an oncolytic virus with natural tropism for cancer cells. We previously showed that RV administration in multiple myeloma (MM) patients was safe, but disease control associated with viral replication in the cancer cells was not observed. The combination with proteasome inhibitors (PIs) has shown to enhance RV therapeutic activity, but the mechanisms of action have not been fully elucidated. Electron microscopy, q-RT-PCR, single-cell mass cytometry (CyTOF), flow cytometry, plaque assays, immunohistochemistry, and Western blot analysis were used to assess RV infection of both myeloma and immune cells. Immune fluorescence, flow cytometry, and luciferase reporter assays were used to assess NF-κB pathway activation upon RV treatments. Immune profiling changes, both ex vivo and in MM patients, were analyzed by flow cytometry and CyTOF analysis. T-cell receptor (TCR) sequencing was also conducted both in immune competent MM mice and in patients enrolled in a phase 1b trial per a standard 3 + 3 dose escalation schedule. Here we show ex vivo and in vivo that proteasome inhibitors (PIs) potentiate reovirus replication in circulating classical monocytes, increasing viral delivery to myeloma cells. We found that the anti-viral signals in monocytes primarily rely on NF-κB activation and that this effect is impaired by the addition of PIs. Conversely, the addition of PIs to RV therapy supports immune activation and killing of MM, independently of direct PI sensitivity. To validate the importance of PIs in enhancing oncolytic viral therapy independently of their killing activity on cancer cells, we then conducted a phase 1b trial of the reovirus Pelareorep together with the PI carfilzomib in 13 heavily pretreated PI-resistant MM patients. Objective responses, which were associated with active reovirus replication in MM cells, T cell activation, and monocytic expansion, were noted in 70% of patients. Although characterized as immunosuppressive drugs, PIs improved RV delivery to MM cells but also enhanced anti-MM efficacy through immune-mediated killing of myeloma cells, independently of their PI sensitivity. These results highlight a more generalizable use of PIs as therapeutic companions to support oncolytic-based therapies in cancers. clinicaltrials.gov, NCT 02101944.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"56 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989829","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":"Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults","authors":"Maike Breidenbach, Peter Bader, Andishe Attarbaschi, Claudia Rossig, Roland Meisel, Markus Metzler, Marion Subklewe, Fabian Mueller, Paul-Gerhardt Schlegel, Irene Teichert von Lüttichau, Jean-Pierre Bourquin, Gabriele Escherich, Gunnar Cario, Peter Lang, Ramona Coffey, Arend von Stackelberg, Semjon Willier, Brigitte Strahm, Christina Peters, Tobias Feuchtinger","doi":"10.1186/s13045-024-01659-x","DOIUrl":"https://doi.org/10.1186/s13045-024-01659-x","url":null,"abstract":"Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood. In this retrospective, multinational study, real-world data were collected from 14 different sites in Germany, Austria and Switzerland on 88 patients receiving 93 2nd-generation CAR therapies. Bridging therapy was classified into the categories 1) no systemic therapy (15/93 treatments), 2) low-intensity therapy (38/93 treatments) and 3) high-intensity therapy (39/93 treatments). We analyzed the impact of bridging regimens on clinical outcome. Patients receiving a high-intensity bridging therapy had a significantly higher tumor burden at time of eligibility compared to patients treated with a low-intensity or no systemic bridging therapy. They suffered significantly more from bacterial adverse events and mucositis. Overall survival was significantly better for patients who did not receive any bridging therapy in comparison to patients who had been treated with a low- or high-intensity bridging regimen. In conclusion, in this retrospective cohort, high-intensity bridging therapy has not improved the outcome in terms of overall and progression-free survival in comparison to a low-intensity therapy. Yet, high-intensity bridging therapy was associated with more adverse events. Our study suggests that a low-intensity bridging regimen may be preferred whenever tumor burden and disease kinetics allow this treatment strategy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988654","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":"Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial","authors":"Jorge E. Cortes, Gail J. Roboz, Maria R. Baer, Brian A. Jonas, Gary J. Schiller, Karen Yee, P. Brent Ferrell, Jay Yang, Eunice S. Wang, William G. Blum, Alice Mims, Hua Tian, Aaron Sheppard, Stéphane de Botton, Pau Montesinos, Antonio Curti, Justin M. Watts","doi":"10.1186/s13045-024-01657-z","DOIUrl":"https://doi.org/10.1186/s13045-024-01657-z","url":null,"abstract":"Olutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1) which induced durable remissions in high-risk, relapsed/refractory (R/R) mIDH1 AML patients in a phase 1/2 trial. We present a pooled analysis from multiple cohorts of the phase 1/2 trial of patients with R/R AML who received combination olutasidenib and azacitidine therapy. Adult patients with mIDH1R132 AML received 150 mg olutasidenib twice daily plus standard-of-care azacitidine (OLU + AZA) and were evaluated for response and safety. Sixty-seven patients with R/R mIDH1R132 AML received combination OLU + AZA. Median age was 66 years (range 28–82) and 54% were male. Most patients (83%) had 2 + prior regimens, including a hypomethylating agent in 40%, IDH1 inhibitor therapy in 31% (olutasidenib in 24%), and hematopoietic stem cell transplant in 10%. Cytogenetic risk was intermediate in 72%, poor in 18% and unknown in 10%. CR/CRh was achieved in 21/67 (31%; 95% CI 21–44) patients, with a median duration of 14.7 months (95% CI 4.6-not reached). CR was achieved in 18/67 (27%; 95% CI 17–39) patients, with median duration of 20.3 months (95% CI 3.7-not reached). Overall response (partial remission or better) was achieved in 34/67 (51%; 95% CI 38–63) patients. Median overall survival was 12.9 months (95% CI 18.7–19.3). In a subset analysis excluding patients who had prior OLU exposure (N = 51), CR/CRh was achieved in 19/51 (37%; 95% CI 24–52) patients, CR was achieved in 16/51 (31%; 95% CI 19–46), and overall response was achieved in 30/51 (59%; 95% CI 44–72). In patients who achieved CR/CRh and were transfusion-dependent at baseline, transfusion independence (RBC and platelets) was achieved in 64% (7/11) and 57% (4/7) of patients, respectively. The most common Grade 3 or 4 adverse events (> 20% patients) were decreased platelet count (37%), red blood cell count (25%), and neutrophil count (24%). Six patients (9%) experienced differentiation syndrome. Four (6%) discontinued treatment due to an adverse event. Olutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R AML with diverse treatment histories. The results represent another therapeutic option for patients with mIDH1 AML who may benefit from a targeted therapy. NCT02719574.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986796","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":"Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition","authors":"Antonino Glaviano, Hannah Si-Hui Lau, Lukas M. Carter, E. Hui Clarissa Lee, Hiu Yan Lam, Elena Okina, Donavan Jia Jie Tan, Wency Tan, Hui Li Ang, Daniela Carbone, Michelle Yi-Hui Yee, Muthu K. Shanmugam, Xiao Zi Huang, Gautam Sethi, Tuan Zea Tan, Lina H. K. Lim, Ruby Yun-Ju Huang, Hendrik Ungefroren, Elisa Giovannetti, Dean G. Tang, Tullia C. Bruno, Peng Luo, Mads Hald Andersen, Bin-Zhi Qian, Jun Ishihara, Derek C. Radisky, Salem Elias, Saurabh Yadav, Minah Kim, Caroline Robert, Patrizia Diana, Kurt A. Schalper, Tao Shi, Taha Merghoub, Simone Krebs, Anjali P. Kusumbe, Matthew S. Davids, Jennifer R. Brown, Alan Prem Kumar","doi":"10.1186/s13045-024-01634-6","DOIUrl":"https://doi.org/10.1186/s13045-024-01634-6","url":null,"abstract":"The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression. By targeting various components of the TME, novel investigational strategies aim to disrupt the TME’s contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME’s implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"42 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974786","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":"Global status and attributable risk factors of breast, cervical, ovarian, and uterine cancers from 1990 to 2021","authors":"Tianye Li, Haoxiang Zhang, Mengyi Lian, Qionghua He, Mingwei Lv, Lingyun Zhai, Jianwei Zhou, Kongming Wu, Ming Yi","doi":"10.1186/s13045-025-01660-y","DOIUrl":"https://doi.org/10.1186/s13045-025-01660-y","url":null,"abstract":"Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively. Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project. From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer. The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940023","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}