华西口腔医学杂志 ›› 2021, Vol. 39 ›› Issue (5): 493-500.doi: 10.7518/hxkq.2021.05.001

• 专家论坛 •    

直接或间接靶向YAP/TAZ治疗头颈部肿瘤的策略选择

冯晓东()   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 中国医学科学院 口腔癌变与防治创新单元 四川大学华西口腔医院,成都 610041
  • 收稿日期:2020-11-24 修回日期:2021-07-17 出版日期:2021-10-01 发布日期:2021-10-11
  • 通讯作者: 冯晓东 E-mail:xiaodongfeng@scu.edu.cn
  • 作者简介:冯晓东,研究员,博士,E-mail:xiaodongfeng@scu.edu.cn
  • 基金资助:
    国家自然科学基金面上项目(81672677);中央高校基本科研业务费专项资金(YJ201987);四川大学华西口腔医院引进人才科研启动经费(QDJF2019-3)

Targeting-YAP/TAZ therapies for head and neck cancer, directly or indirectly?

Feng Xiaodong.()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management & West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2020-11-24 Revised:2021-07-17 Online:2021-10-01 Published:2021-10-11
  • Contact: Feng Xiaodong. E-mail:xiaodongfeng@scu.edu.cn
  • Supported by:
    The National Natural Science Foundation of China(81672677);The Fundamental Research Funds for the Central Universities(YJ201987);The Scientific Research Foundation for Recruited Talents-West China Hospital of Stomatology, Sichuan University(QDJF2019-3);Correspondence: Feng Xiaodong, E-mail: xiaodongfeng@scu.edu.cn

摘要:

YAP/ TAZ在头颈肿瘤中普遍异常激活,且对肿瘤生长调控意义重大,故直接靶向YAP/TAZ在头颈部肿瘤治疗中具有极高的潜能。但是随着研究的深入,该策略的局限性也逐步体现,主要表现为两点:1)受限于当前技术水平,暂时还没有发展出安全特异的YAP/TAZ转录辅助激活抑制剂;2)YAP/TAZ调控正常细胞增殖和生存、维持组织成体干细胞的自我更新、参与器官发育、组织大小调节、组织再生等重要生理进程,直接靶向YAP/TAZ可能对这些重要的正常生理活动造成不良影响,存在较大的策略风险。值得注意的是,YAP/TAZ在头颈肿瘤中的异常分子变化比例有限,其异常激活主要源于上游异常分子事件。因此通过研究YAP/TAZ在头颈肿瘤中激活的上游异常分子事件及调控机制,或可为间接靶向YAP/TAZ治疗头颈部肿瘤提供广阔前景。

关键词: YAP, TAZ, Hippo, 头颈部肿瘤, 靶向治疗

Abstract:

YAP/TAZ are wild over-activated in head and neck squamous cell carcinoma (HNSCC) with high potential as a direct therapy target for HNSCC treatments. However, the efforts on the directly targeting-YAP/TAZ therapies over the past decade, have very limited impacts, mainly caused by: 1. There is still none effective and specific YAP/TAZ inhibitor with clinical potential; 2. YAP/TAZ might not be directly targeted, because of their multiple important biological functions, such as: regulation of cell proliferation and survival, stem cell maintain, regulation of organ development, organ size control, and tissue regeneration. Interestingly, the over-activation of YAP/TAZ in HNSCC mainly be regulated by upstream abnormal molecular or biological events, instead of genes alteration of YAP/TAZ. Therefore, exploring the alternative molecular events regulating YAP/TAZ activation and molecular mechanism in HNSCC might help to uncover novel indirect targets of YAP/TAZ therapies for HNSCC prevention and treatment.

Key words: YAP, TAZ, Hippo, head and neck cancer, targeting therapies

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