School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Department of Otolaryngology, University of California, San Francisco, USA.
Biochim Biophys Acta Mol Cell Res. 2020 Jun;1867(6):118679. doi: 10.1016/j.bbamcr.2020.118679. Epub 2020 Feb 19.
Head and neck squamous cell carcinoma (HNSCC) is a highly morbid, genetically unstable disease derived from the mucoepithelium of the upper aerodigestive tract. Recent characterization of this disease has implicated the PI3K-Akt-mTOR pathway as one of the most frequently dysregulated pathways. As such, there are several classes of PI3K inhibitors currently undergoing clinical trials. In this article, we review the PI3K pathway, mutations of this pathway in HNSCC, drugs that target PI3K, the impact of these agents on the PI3K and GSK-3 signaling axes, ongoing clinical trials evaluating PI3K inhibitors, and the challenges of using these drugs in the clinic. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.
头颈部鳞状细胞癌（HNSCC）是一种高度致命的、遗传不稳定的疾病，来源于上呼吸道的黏膜上皮。最近对这种疾病的特征描述表明，PI3K-Akt-mTOR 通路是最常失调的通路之一。因此，目前有几类 PI3K 抑制剂正在进行临床试验。在本文中，我们回顾了 PI3K 通路、HNSCC 中该通路的突变、针对 PI3K 的药物、这些药物对 PI3K 和 GSK-3 信号轴的影响、正在评估 PI3K 抑制剂的临床试验，以及在临床中使用这些药物的挑战。本文是由 James McCubrey、Agnieszka Gizak 和 Dariusz Rakus 编辑的题为“GSK-3 和相关激酶在癌症、神经和其他疾病中的作用”的特刊的一部分。
