Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms

doi:10.1016/j.neo.2024.100996

科研成果详情

题名	Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms
作者	Xu, Qianqian 1,2; Wang, Jiaqi 1,2; Mao, Yuting1,2; Xuan, Ziyang1,2; Yang, Ke 1; Tang, Xi 1; Zhu, Xin1,2
发表日期	2024-06
发表期刊	Neoplasia (New York, N.Y.) 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	BRAFV600E Metabolomics PIM1 Synergism Thyroid carcinoma
其他关键词	EXPRESSION ; KINASE ; MELANOMA ; GROWTH ; CANCER
摘要	Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment.
资助项目	National Natural Science Foundation of China[82072950];Zhejiang Cancer Hospital[IRB-2023-438];
出版者	ELSEVIER SCIENCE INC
ISSN	1476-5586
EISSN	1476-5586
卷号	52
DOI	10.1016/j.neo.2024.100996
页数	10
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:001224890500001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38593698
SCOPUSEID	2-s2.0-85189795537
通讯作者地址	[Zhu, Xin]Key Laboratory of Head & Neck Cancer Translation Research of Zhejiang Province,Zhejiang Cancer Hospital,Hangzhou,China
Scopus学科分类	Cancer Research
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/211103
专题	其他_浙江省肿瘤医院（浙江省癌症中心）
通讯作者	Zhu, Xin
作者单位	1.Key Laboratory of Head & Neck Cancer Translation Research of Zhejiang Province,Zhejiang Cancer Hospital,Hangzhou,China; 2.Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital),Hangzhou,310022,China
第一作者单位	温州医科大学
推荐引用方式 GB/T 7714	Xu, Qianqian,Wang, Jiaqi,Mao, Yuting,et al. Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms[J]. Neoplasia (New York, N.Y.),2024,52.
APA	Xu, Qianqian., Wang, Jiaqi., Mao, Yuting., Xuan, Ziyang., Yang, Ke., ... & Zhu, Xin. (2024). Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms. Neoplasia (New York, N.Y.), 52.
MLA	Xu, Qianqian,et al."Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms".Neoplasia (New York, N.Y.) 52(2024).