PI3K抑制剂在淋巴瘤治疗中的现状和挑战

doi:10.3760/cma.j.cn371439-20240407-00111

摘要/Abstract

摘要：

磷脂酰肌醇3-激酶（PI3K）信号通路异常活化是恶性淋巴瘤发病机制之一，PI3K抑制剂是近年来淋巴瘤治疗的新靶点，目前已开发出多种不同类型的PI3K抑制剂，部分药物已经上市，部分药物仍处于临床试验阶段。PI3K抑制剂存在多种不良反应，提高安全性和有效性是PI3K抑制剂未来研发的重要方向。

关键词: 磷酸肌醇3-激酶类, 淋巴瘤, 药物相关性副作用和不良反应, 抑制剂

Abstract:

Abnormal activation of phosphoinositide 3-kinase （PI3K） pathway is one of the pathogenesis of malignant lymphoma. PI3K inhibitors are new targets for lymphoma treatment in recent years. At present， a variety of different types of PI3K inhibitors have been developed， some of which have been approved for clinical use， and some are still in clinical trials. PI3K inhibitors have multiple side effects. Improving safety and efficacy is an important direction for the future development of PI3K inhibitors.

Key words: Phosphatidylinositol 3-kinases, Lymphoma, Drug-related side effects and adverse reactions, Inhibitors

付瑛, 王华庆. PI3K抑制剂在淋巴瘤治疗中的现状和挑战[J]. 国际肿瘤学杂志, 2024, 51(10): 660-666.

Fu Ying, Wang Huaqing. PI3K inhibitors in the treatment of lymphoma： present and challenges[J]. Journal of International Oncology, 2024, 51(10): 660-666.

图/表 1

表1

部分正在进行中的PI3K抑制剂治疗淋巴瘤临床试验信息"

药品名称	研发公司	注册号	注册题目	适应证	靶点	开始日期
INCB-040093^[32]	美国Incyte公司	NCT01905813	A phase 1， open-label， dose escalation， safety and tolerability study of INCB-040093 in subjects with previously treated B-cell malignancies	B细胞恶性肿瘤	PI3Kδ	2013/6/30
parsaclisib^[33]	美国Incyte公司	NCT03126019	A phase 2， multicenter， open-label study of INCB050465， a PI3Kδ inhibitor in relapsed or refractory follicular lymphoma (CITADEL-203)	复发或难治性FL	PI3Kδ	2017/4/24
SHC014748^[34]	南京圣和药业股份有限公司	CTR20180988	SHC014748M在惰性B细胞恶性血液肿瘤患者中的Ⅰ期临床研究	复发或难治性惰性 B细胞恶性血液肿瘤	PI3Kδ	2018/7/2
IOA-244^[35]	瑞士iOnctura 公司	NCT04328844	First-in-human dose study of IOA-244 alone and in combination with pemetrexed/cisplatin in patients with advanced or metastatic cancers	成人非霍奇金淋巴瘤	PI3Kδ	2020/2/25
TQ-B3525^[36]	正大天晴药业集团股份有限公司	CTR20200426	TQ-B3525治疗FL临床试验	复发或难治性FL	PI3Kγ/ PI3Kδ	2020/3/23
HMPL-689^[37]	上海和黄药业有限公司	CTR20210264	HMPL-689治疗复发/难治MZL和FL的临床研究	复发/难治性MZL和FL	PI3Kγ/ PI3Kδ	2021/2/18
linperlisib （YY- 20394）230^[38]	上海璎黎药业有限公司	CTR20210333	YY-20394在复发和（或）难治性外周T/NK细胞淋巴瘤患者中的Ⅱ期临床试验	复发和（或）外周难治性 T/NK细胞淋巴瘤	PI3Kδ	2021/3/12
BGB-10188^[39]	百济神州（北京）生物科技有限公司	CTR20220463	一项BGB-10188（一种PI3Kδ抑制剂）联合泽布替尼治疗成熟B细胞恶性肿瘤患者以及联合替雷利珠单抗治疗实体瘤患者的剂量递增和扩展1/2期研究	CLL、SLL、FL、MZL、套细胞淋巴瘤、弥漫性大B细胞淋巴瘤、晚期实体瘤、非小细胞肺癌、小细胞肺癌、转移性黑素瘤	PI3Kδ	2022/3/14

表1

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