Characterizing and Targeting of BCL-2 Family Members in Nasopharyngeal Carcinoma.

IF 2.3 3区医学 Q1 OTORHINOLARYNGOLOGY

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck Pub Date : 2024-10-30 DOI:10.1002/hed.27973

A A Thai, R J Young, M Bressel, G L Kelly, N Sejic, S W Tsao, A Trigos, D Rischin, B J Solomon

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Abstract

Background: The success of BH3 mimetics in hematological malignancies has spurred interest in their application in solid tumors. We examined the expression of the BCL-2 family of molecules in NPC tumors and cell lines and explored the anticancer efficacy of BH3 mimetics in vitro.

Methods: Immunohistochemistry for BCL-2, MCL-1, BCL-xL, and transcriptomic analyses was conducted on NPC tumors. The efficacy of ABT-199, S63845, and ABT-737 were examined as monotherapy and in combination with cisplatin in NPC cell lines. RNA sequencing was performed to identify up and downregulated pathways in sensitive cell lines.

Results: One hundred and forty-nine EBV-positive NPC and 15 EBV-negative NPC were identified. Expression of BCL-2 was more frequent in EBV-positive NPC. BCL-2, MCL-1, and BCL-xL expression was not prognostic for overall survival. Marked sensitivity was seen with the combination of S63845 and cisplatin in NPC43.

Conclusion: Our study demonstrates the therapeutic potential of combining cisplatin and S63845, which warrants further investigation.

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鼻咽癌中 BCL-2 家族成员的特征和靶向研究

背景：BH3模拟物在血液恶性肿瘤中的成功应用激发了人们对其在实体瘤中应用的兴趣。我们研究了鼻咽癌肿瘤和细胞系中 BCL-2 家族分子的表达情况，并探索了 BH3 拟分子在体外的抗癌疗效：方法：对鼻咽癌肿瘤进行BCL-2、MCL-1、BCL-xL免疫组化和转录组分析。在鼻咽癌细胞系中检测了 ABT-199、S63845 和 ABT-737 作为单一疗法以及与顺铂联合疗法的疗效。对敏感细胞系进行了 RNA 测序，以确定上调和下调的通路：结果：共鉴定出 149 例 EBV 阳性鼻咽癌细胞系和 15 例 EBV 阴性鼻咽癌细胞系。在EBV阳性的鼻咽癌中，BCL-2的表达更为频繁。BCL-2、MCL-1和BCL-xL的表达对总生存率没有预示作用。S63845和顺铂联合治疗鼻咽癌43具有明显的敏感性：我们的研究证明了顺铂和 S63845 联用的治疗潜力，值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck 医学-耳鼻喉科学

CiteScore

7.00

自引率

6.90%

发文量

278

审稿时长

1.6 months

期刊介绍： Head & Neck is an international multidisciplinary publication of original contributions concerning the diagnosis and management of diseases of the head and neck. This area involves the overlapping interests and expertise of several surgical and medical specialties, including general surgery, neurosurgery, otolaryngology, plastic surgery, oral surgery, dermatology, ophthalmology, pathology, radiotherapy, medical oncology, and the corresponding basic sciences.