从“合成致死”策略的视角浅谈头颈鳞癌靶向治疗

doi:10.19438/j.cjoms.2021.03.019

中国口腔颌面外科杂志 ›› 2021, Vol. 19 ›› Issue (3): 278-283.doi: 10.19438/j.cjoms.2021.03.019

从“合成致死”策略的视角浅谈头颈鳞癌靶向治疗

陈澜, 张志愿, 孙树洋

上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科,上海交通大学口腔医学院, 国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海 200011

收稿日期:2020-12-17 修回日期:2021-01-19 发布日期:2021-07-16
通讯作者: 孙树洋,E-mail：sunshuyang@sjtu.edu.cn
作者简介:陈澜（1995-）,女,硕士,E-mail: lanchen@sjtu.edu.cn
基金资助:
国家重点研发计划（2017YFC0908500）; 国家自然科学基金重点项目（82030085）

Synthetic lethality: towards the targeted strategies of head and neck squamous cell carcinoma

CHEN Lan, ZHANG Zhi-yuan, SUN Shu-yang

Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China

Received:2020-12-17 Revised:2021-01-19 Published:2021-07-16

摘要/Abstract

摘要： 合成致死指在2个基因中,单独1个基因发生功能性缺失不影响细胞存活,但是2个基因同时发生功能性缺失,能够特异性诱导细胞死亡。头颈鳞癌是以抑癌基因高频突变为特征的恶性肿瘤,利用合成致死能够为该类靶向药物匮乏的肿瘤提供全新的治疗策略。得益于RNA干扰技术和CRISPR/Cas9基因编辑技术的发展,肿瘤合成致死筛选变得更加精准高效,开辟了全基因组范围内筛选抗肿瘤合成致死新靶点,完善了联合用药方案和逆转肿瘤免疫逃逸等治疗策略。由于合成致死具有强烈的遗传背景依赖性,人源性肿瘤异种移植瘤模型能够充分反映肿瘤异质性和患者的遗传学背景,是进行合成致死筛选和验证的理想临床前模型。

关键词: 合成致死, 头颈鳞癌, 抑癌基因, 靶向治疗

Abstract: Synthetic lethality occurs between two genes when loss of function of either gene is viable but loss of function of both genes simultaneously specifically induces cell death. Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor characterized by high-frequency mutations of tumor suppressor genes, and synthetic lethality has the potential to provide a novel therapeutic strategy for HNSCC which lacks of targeted drugs. With the development of RNA interfering and CRISPR/Cas9-mediated gene editing technology, synthetic lethal screening tends to be more accurate and efficient to explore therapeutic approach including screening novel anti-tumor targets at the whole genome region, refining combination drug therapy and reversing tumor immune escape. Considering genetic context significantly influences synthetic lethality, patient-derived xenograft (PDX) model performs as an ideal preclinical model for screening and verifying synthetic lethality, because it can fully reflect tumor heterogeneity and genetic background of patients.

Key words: Synthetic lethality, Head and neck squamous cell carcinoma, Tumor suppressor gene, Targeted therapy

中图分类号:

R739.8

陈澜, 张志愿, 孙树洋. 从“合成致死”策略的视角浅谈头颈鳞癌靶向治疗[J]. 中国口腔颌面外科杂志, 2021, 19(3): 278-283.

CHEN Lan, ZHANG Zhi-yuan, SUN Shu-yang. Synthetic lethality: towards the targeted strategies of head and neck squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2021, 19(3): 278-283.

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从“合成致死”策略的视角浅谈头颈鳞癌靶向治疗

Synthetic lethality: towards the targeted strategies of head and neck squamous cell carcinoma

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