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

doi:10.7518/hxkq.2021.05.001

Abstract

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

CLC Number:

R 782

Feng Xiaodong.. Targeting-YAP/TAZ therapies for head and neck cancer, directly or indirectly?[J]. West China Journal of Stomatology, 2021, 39(5): 493-500.

Figures/Tables 5

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名称	靶点	活性	模型	文献/专利
维替泊芬	YAP-TEAD相互作用（机制并不完全清楚）	TEAD转录活性降低	葡萄膜黑色素瘤（体内、体外）；视网膜母细胞瘤	[16,33-35]
CA3	抑制方式和与YAP相互作用的机制仍然未知	调节YAP/TEAD转录活性并降低YAP表达	食管腺癌（体内、体外）	[36]
芴-肟化合物类似物	机制并不完全清楚	降低YAP报告基因的活性	无	[37-38]
基于双芳基肼支架化合物	YAP/TAZ-TEAD相互作用（机制并不完全清楚）	TEAD-GAL4激活试验中中度活性；高浓度下对间皮瘤细胞系的抗增殖活性	间皮瘤细胞系（体外）	[39-40]
小分子抑制剂 WO2017/053706	TEAD核心的脂质囊	抑制靶基因表达和细胞增殖	肝细胞系	[41]
氟灭酸	TEAD核心的脂质囊	TEAD报告基因活性和一些Hippo通路反应基因活性下降	乳腺癌细胞系	[42]
氟灭酸衍生物/TED-347	YAP/TAZ-TEAD相互作用	YAP-TEAD相互作用，转录活性降低	胶质母细胞瘤细胞系	[43]
环状YAP样肽	内源性YAP竞争	TEAD-YAP结合被抑制，YAP-TEAD转录活性	无	[30]
super-TDU	与YAP直接竞争TEAD的结合，抑制YAP的活性	TEAD-YAP结合被抑制	胃癌、结直肠癌、肺癌（体内、体外）	[31-32]
CPD3.1	破坏YAP-TEAD蛋白质-蛋白质相互作用	抑制TEAD活性	HeLa体外	[43-44]
Peptide 17/yap样多肽（17mer）	破坏YAP-TEAD蛋白质-蛋白质相互作用	YAP-TEAD转录活性降低	肝癌（体内外）、骨肉瘤（体外）	[30-45]
雷公藤红素	直接与YAP/TAZ TEAD相互作用并破坏其作用	YAP/TEAD转录活性降低	肺癌、乳腺癌（体外）	[46]

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