Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution

doi:10.21037/tcr-21-50

HFCAS OpenIR

	Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution
	Yu, Haifeng 1,2; Kong, Haiying 3; Li, Cong 1,2; Dong, Xiaowu 4; Wu, Yizhe 4; Zhuang, Yuxin 4; Han, Shuiyun 1,2; Lei, Tao 1,2; Yang, Haiyan 1,2
	2021-05-01
发表期刊	TRANSLATIONAL CANCER RESEARCH
ISSN	2218-676X
通讯作者	Lei, Tao(leitao070713@sohu.com) ; Yang, Haiyan(haiyanyang1125@163.com)
摘要	Background: Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma confined to central nervous system. Current treatments including surgery, chemotherapy and whole-brain radiotherapy often fail to achieve satisfactory effect, especially in elderly. As a regimen in targeted therapy, Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been tested in several clinical trials against PCNSL, offering hope for patients unfit for chemotherapy. We aim to evaluate and compare the anti-PCNSL ability of three different BTK inhibitors, ibrutinib, zanubrutinib and tirabrutinib, providing direct evidence for the targeted therapy of PCNSL. Methods: Retrospective study was done on patients who received ibrutinib-based therapy in our hospital. Cerebrospinal fluid (CSF) from one patient was collected to measure the concentration of ibrutinib. Inhibition assay and apoptosis assay were done on lymphoma cells to determine the anti-tumoral effects of three inhibitors. Pharmacokinetic study was conducted to evaluate their ability in penetrating blood brain barrier and distributing in brain. Results: In retrospective study, we found three patients with PCNSL who had good clinical response to ibrutinib-based therapy (2 complete remission, 1 partial remission), which further support the use of BTK inhibitors in PCNSL. In vitro studies show that ibrutinib has the best anti-tumoral ability among three inhibitors. In vivo study on pharmacokinetic profiles indicate that both ibrutinib and tirabrutinib are good in distributing in brain parenchyma. Conclusions: In conclusion, our study results suggest that BTK inhibitors can be promising candidates for PCNSL treatment, preferring the use of ibrutinib and tirabrutinib as anti-PCNSL agents among the three inhibitors.
关键词	Primary central nervous system lymphoma ( PCNSL) Bruton's tyrosine kinase (BTK) ibrutinib zanubrutinib tirabrutinib
DOI	10.21037/tcr-21-50
关键词[WOS]	IBRUTINIB ; CHALLENGE
收录类别	SCI
语种	英语
资助项目	Science and Technology Program of Traditional Chinese Medicinee, and Zhejiang[2021ZB038] ; Zhejiang Provincial Medicine and Health Science Fund[2021KY105]
项目资助者	Science and Technology Program of Traditional Chinese Medicinee, and Zhejiang ; Zhejiang Provincial Medicine and Health Science Fund
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000656696500003
出版者	AME PUBL CO
引用统计	被引频次：13[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/123763
专题	中国科学院合肥物质科学研究院
通讯作者	Lei, Tao; Yang, Haiyan
作者单位	1.Univ Chinese Acad Sci, Dept Lymphoma, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 2.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China 3.Hangzhou Hanggang Hosp, Dept Pharm, Zhejiang Med & Hlth Grp, Hangzhou Hosp, Hangzhou, Peoples R China 4.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou Inst Innovat Med, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Yu, Haifeng,Kong, Haiying,Li, Cong,et al. Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution[J]. TRANSLATIONAL CANCER RESEARCH,2021,10.
APA	Yu, Haifeng.,Kong, Haiying.,Li, Cong.,Dong, Xiaowu.,Wu, Yizhe.,...&Yang, Haiyan.(2021).Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution.TRANSLATIONAL CANCER RESEARCH,10.
MLA	Yu, Haifeng,et al."Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution".TRANSLATIONAL CANCER RESEARCH 10(2021).