PI3K inhibitor idelalisib enhances the anti-tumor effects of CDK4/6 inhibitor palbociclib via PLK1 in B-cell lymphoma

被引：1

作者：

Hu, Dingyao ^{[1
]}

Cao, Jiaowu ^{[1
]}

Yu, Hui ^{[1
]}

Ding, Ning ^{[1
]}

Mi, Lan ^{[1
]}

Ye, Yingying ^{[1
]}

Li, Miaomiao ^{[1
]}

Wang, Dedao ^{[1
]}

Wu, Jiajin ^{[1
]}

Wang, Xiaogan ^{[1
]}

Song, Yuqin ^{[1
]}

Zhu, Jun ^{[1
]}

Ping, Lingyan ^{[1
]}

机构：

[1] Peking Univ Canc Hosp & Inst, Dept Lymphoma, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100142, Peoples R China

来源：

CANCER LETTERS | 2024年 / 597卷

基金：

北京市自然科学基金;

关键词：

B cell lymphoma; CDK4/6; inhibitor; PI3K inhibitor; Combination therapy; DEPENDENT KINASE INHIBITOR; CYCLE; CANCER; PATHOGENESIS; PI3K-DELTA; ARREST; CDC25A;

D O I：

10.1016/j.canlet.2024.216996

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Relapsed or refractory diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) patients still faced with poor survival, representing an unmet clinical need. In-depth research into the disease's pathogenesis and the development of targeted treatment strategies are urgently needed. Here, we conducted a comprehensive bioinformatic analysis of gene mutation and expression using data from our center and public databases. Cell cycle-related genes especially for CDKN2A/B-CDK4/6/CCND1 machinery altered frequently in DLBCL and MCL. Clinically, high CDK4 and CDK6 expression were correlated with poor prognosis of DLBCL and MCL patients. Furthermore, we also validated the pharmacological efficacy of CDK4/6 inhibitor palbociclib and its synergy effect with PI3K inhibitor idelalisib utilizing in vitro cell lines and in vivo cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Our results provided sufficient pre-clinical evidence to support the potential combination of palbociclib and idelalisib for DLBCL and MCL patients.

引用

页数：15

共 60 条

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