Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune therapies.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-08-13 DOI:10.1038/s41420-025-02678-4

David Kegyes, Andrei Tat, Alin Stefan Vizitiu, Daiana Vazar-Tripon, Radu Ilie, Adrian Bogdan Tigu, Diana Cenariu, Anamaria Bancos, Sabina Iluta, Ciprian Jitaru, Madalina Nistor, Radu Tomai, Diana Gulei, Mihnea Zdrenghea, Hermann Einsele, Gabriel Ghiaur, Carlo M Croce, Ciprian Tomuleasa

{"title":"Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune therapies.","authors":"David Kegyes, Andrei Tat, Alin Stefan Vizitiu, Daiana Vazar-Tripon, Radu Ilie, Adrian Bogdan Tigu, Diana Cenariu, Anamaria Bancos, Sabina Iluta, Ciprian Jitaru, Madalina Nistor, Radu Tomai, Diana Gulei, Mihnea Zdrenghea, Hermann Einsele, Gabriel Ghiaur, Carlo M Croce, Ciprian Tomuleasa","doi":"10.1038/s41420-025-02678-4","DOIUrl":null,"url":null,"abstract":"<p><p>A hallmark of cancer biology is resistance to apoptosis. BCL-2 is an anti-apoptotic molecule that is being overexpressed in several myeloid diseases, such as acute myeloid leukemia and myelodysplastic syndromes, but also in several lymphoid cancers, such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphomas and multiple myeloma. Venetoclax (VEN) is a BCL-2 small molecule inhibitor. Data about its structure, biochemical characteristics and in vitro efficacy against several blood cancer cell lines were first reported in 2013. Shortly after, the first clinical trials reported that single-agent VEN provides no long-term survival benefits. In contrast, when used in combination, VEN led to significantly improved outcomes and eventually to its first US FDA approvals in 2018. As the modern approach to treating hematological malignancies are the chemotherapy-free regimen, in the current manuscript, we provide a comprehensive view on all available therapies that are considered to be chemotherapy-free, with a special emphasis on acute myeloid leukemia (AML), where phase I-III clinical trials have provided the most data.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"379"},"PeriodicalIF":7.0000,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350645/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02678-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

A hallmark of cancer biology is resistance to apoptosis. BCL-2 is an anti-apoptotic molecule that is being overexpressed in several myeloid diseases, such as acute myeloid leukemia and myelodysplastic syndromes, but also in several lymphoid cancers, such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphomas and multiple myeloma. Venetoclax (VEN) is a BCL-2 small molecule inhibitor. Data about its structure, biochemical characteristics and in vitro efficacy against several blood cancer cell lines were first reported in 2013. Shortly after, the first clinical trials reported that single-agent VEN provides no long-term survival benefits. In contrast, when used in combination, VEN led to significantly improved outcomes and eventually to its first US FDA approvals in 2018. As the modern approach to treating hematological malignancies are the chemotherapy-free regimen, in the current manuscript, we provide a comprehensive view on all available therapies that are considered to be chemotherapy-free, with a special emphasis on acute myeloid leukemia (AML), where phase I-III clinical trials have provided the most data.

查看原文本刊更多论文

venetoclax联合靶向和/或免疫疗法治疗急性髓系白血病的无化疗综合观察

癌症生物学的一个特征是对细胞凋亡的抵抗。BCL-2是一种抗凋亡分子，在多种髓系疾病中过度表达，如急性髓系白血病和骨髓增生异常综合征，但也在多种淋巴系癌症中过度表达，如急性淋巴母细胞白血病、慢性淋巴细胞白血病、非霍奇金淋巴瘤和多发性骨髓瘤。Venetoclax （VEN）是一种BCL-2小分子抑制剂。2013年首次报道了其结构、生化特性及对多种血癌细胞系体外疗效的数据。不久之后，首次临床试验报告单药VEN不能提供长期生存益处。相比之下，当联合使用时，VEN显着改善了结果，并最终在2018年获得了美国FDA的首次批准。由于治疗血液系统恶性肿瘤的现代方法是无化疗方案，在目前的手稿中，我们提供了一个全面的观点，所有可用的治疗被认为是无化疗的，特别强调急性髓性白血病（AML），其中I-III期临床试验提供了最多的数据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.