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

Xiao-Dong Feng
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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.

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靶向yap /TAZ治疗头颈癌,直接还是间接?
YAP/TAZ在头颈部鳞状细胞癌(HNSCC)中过度激活,具有很高的潜力作为HNSCC治疗的直接治疗靶点。然而,近十年来在直接靶向yap /TAZ治疗方面的努力,影响非常有限,主要原因是:1。目前仍没有临床潜力的有效特异性YAP/TAZ抑制剂;2. 由于YAP/TAZ具有多种重要的生物学功能,如:调节细胞增殖和存活、干细胞维持、调节器官发育、控制器官大小和组织再生,因此可能无法直接靶向。有趣的是,在HNSCC中,YAP/TAZ的过度激活主要受上游异常分子或生物学事件的调控,而不是YAP/TAZ基因的改变。因此,探索HNSCC中调节YAP/TAZ激活的其他分子事件及其分子机制可能有助于发现YAP/TAZ治疗HNSCC的新的间接靶点。
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