Kegyes David, Tat Andrei, Vizitiu Alin Stefan, Vazar-Tripon Daiana, Ilie Radu, Tigu Adrian Bogdan, Cenariu Diana, Bancos Anamaria, Iluta Sabina, Jitaru Ciprian, Nistor Madalina, Tomai Radu, Gulei Diana, Zdrenghea Mihnea, Einsele Hermann, Ghiaur Gabriel, Croce Carlo M, Tomuleasa Ciprian
Department of Personalized Medicine and Rare Diseases, Medfuture Institute for Biomedical Research - Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Oncology, Bistrita Emergency Hospital, Bistrita, Romania.
Cell Death Discov. 2025 Aug 13;11(1):379. doi: 10.1038/s41420-025-02678-4.
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.
癌症生物学的一个标志是对细胞凋亡的抗性。BCL-2是一种抗凋亡分子，在几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，也在几种淋巴癌中过度表达，如急性淋巴细胞白血病、慢性淋巴细胞白血病、非霍奇金淋巴瘤和多发性骨髓瘤。维奈克拉（VEN）是一种BCL-2小分子抑制剂。关于其结构、生化特性以及对几种血液癌细胞系的体外疗效的数据于2013年首次报道。此后不久，首批临床试验报告称，单药VEN未提供长期生存益处。相比之下，联合使用时，VEN导致显著改善的结果，并最终在2018年首次获得美国食品药品监督管理局（FDA）批准。由于现代治疗血液系统恶性肿瘤的方法是无化疗方案，在本手稿中，我们全面介绍了所有被认为是无化疗的可用疗法，特别强调了急性髓系白血病（AML），其中I-III期临床试验提供了最多的数据。
