磷脂酰肌醇 3-激酶抑制剂在慢性淋巴细胞白血病治疗中的应用进展。
The Evolving Use of Phosphatidylinositol 3-Kinase Inhibitors for the Treatment of Chronic Lymphocytic Leukemia.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, CLL Center, 450 Brookline Avenue, Boston, MA 02215, USA.
出版信息
Hematol Oncol Clin North Am. 2021 Aug;35(4):807-826. doi: 10.1016/j.hoc.2021.03.009. Epub 2021 May 27.
Abstract
B cells express 4 phosphatidylinositol 3-kinase (PI3K) isoforms and have a dependence on p110δ for survival. The design of isoform-selective inhibitors is possible, and pharmacologic inhibition of p110δ is toxic to neoplastic chronic lymphocytic leukemia (CLL) cells for both cell-intrinsic and cell-extrinsic reasons. Idelalisib is a first-in-class p110δ inhibitor that exhibits efficacy for the treatment of relapsed CLL irrespective of adverse prognostic features. Duvelisib is a p110γ/δ inhibitor with a similar efficacy and safety profile to idelalisib. Recent data indicate that umbralisib, a p110δ/CK-1ε dual inhibitor, is safe and effective when administered to patients with CLL.
摘要
B 细胞表达 4 种磷脂酰肌醇 3-激酶（PI3K）同工型，并且依赖于 p110δ 来维持生存。同工型选择性抑制剂的设计是可行的，并且 p110δ 的药理学抑制对肿瘤性慢性淋巴细胞白血病（CLL）细胞具有内在和外在的毒性。Idelalisib 是一种首创的 p110δ 抑制剂，无论不良预后特征如何，对复发性 CLL 的治疗均有效。Duvelisib 是一种 p110γ/δ 抑制剂，其疗效和安全性与 idelalisib 相似。最近的数据表明，当给予 CLL 患者时，p110δ/CK-1ε 双重抑制剂 umbralisib 是安全有效的。
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