Sillar Jonathan R, Enjeti Anoop K
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia.
Haematology Department, Calvary Mater Hospital Newcastle, Waratah, NSW 2298, Australia.
Cancers (Basel). 2019 Oct 26;11(11):1660. doi: 10.3390/cancers11111660.
Acute Myeloid Leukaemia is a devastating disease that continues to have a poor outcome for the majority of patients. In recent years, however, a number of drugs have received FDA approval, following on from successful clinical trial results. This parallels the characterization of the molecular landscape of Acute Myeloid Leukaemia (AML) over the last decade, which has led to the development of drugs targeting newly identified recurring mutations. In addition, basic biological research into the pathobiology of AML has identified aberrant programmed cell death pathways in AML. Following on from successful outcomes in lymphoid malignancies, drugs targeting the B Cell Lymphoma 2 (BCL-2) family of anti-apoptotic proteins have been explored in AML. In this review, we will outline the preclinical and clinical work to date supporting the role of drugs targeting BCL-2, with Venetoclax being the most advanced to date. We will also highlight rationale combinations using Venetoclax, ongoing clinical trials and biomarkers of response identified from the early phase clinical trials performed.
急性髓系白血病是一种毁灭性疾病，大多数患者的预后仍然很差。然而，近年来，一些药物在临床试验取得成功结果后获得了美国食品药品监督管理局（FDA）的批准。这与过去十年对急性髓系白血病（AML）分子格局的特征描述相平行，该描述促使了针对新发现的复发性突变的药物研发。此外，对AML病理生物学的基础生物学研究发现了AML中异常的程序性细胞死亡途径。继在淋巴系统恶性肿瘤中取得成功后，针对抗凋亡蛋白B细胞淋巴瘤2（BCL-2）家族的药物已在AML中进行了探索。在本综述中，我们将概述迄今为止支持靶向BCL-2药物作用的临床前和临床研究工作，维奈托克是目前进展最为领先的药物。我们还将重点介绍使用维奈托克的合理联合方案、正在进行的临床试验以及从早期临床试验中确定的反应生物标志物。
