Zhang Yuxi, Sun Xinchen
The First School of Clinical Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Onco Targets Ther. 2020 Oct 9;13:10207-10220. doi: 10.2147/OTT.S270342. eCollection 2020.
Head and neck cancers are one of the most prevalent cancers globally. Among them, head and neck squamous cell carcinoma (HNSCC) accounts for approximately 90% of head and neck cancers, which occurs in the oral cavity, oral pharynx, hypopharynx and larynx. The 5-year survival rate of HNSCC patients is only 63%, mainly because about 80-90% of patients with advanced HNSCC tend to suffer from local recurrence or even distant metastasis. Despite the more in-depth understanding of the molecular mechanisms underlying the occurrence and progression of HNSCC in recent years, effective targeted therapies are unavailable for HNSCC, which emphasize the urgent demand for studies in this area. Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase that contributes to oncogenesis and tumor progression by its significant function in cell survival, proliferation, adhesion, invasion and migration. In addition, FAK exerts an effect on the tumor microenvironment, epithelial-mesenchymal transition, radiation (chemotherapy) resistance, tumor stem cells and regulation of inflammatory factors. Moreover, the overexpression and activation of FAK are detected in multiple types of tumors, including HNSCC. FAK inhibition can induce cell cycle arrest and apoptosis, significantly decrease cell growth, invasion and migration in HNSCC cell lines. In this article, we mainly review the research progress of FAK in the occurrence, development and metastasis of HNSCC, and put forward the prospects for the therapeutic targets of HNSCC.
头颈癌是全球最常见的癌症之一。其中,头颈部鳞状细胞癌(HNSCC)约占头颈癌的90%,发生于口腔、口咽、下咽和喉。HNSCC患者的5年生存率仅为63%,主要原因是约80 - 90%的晚期HNSCC患者易发生局部复发甚至远处转移。尽管近年来对HNSCC发生和进展的分子机制有了更深入的了解,但目前尚无有效的HNSCC靶向治疗方法,这凸显了该领域研究的迫切需求。粘着斑激酶(FAK)是一种细胞内非受体酪氨酸激酶,通过其在细胞存活、增殖、粘附、侵袭和迁移中的重要作用,促进肿瘤发生和进展。此外,FAK还对肿瘤微环境、上皮-间质转化、放射(化学)抗性、肿瘤干细胞及炎症因子调节产生影响。而且,在包括HNSCC在内的多种肿瘤中均检测到FAK的过表达和激活。抑制FAK可诱导细胞周期停滞和凋亡,显著降低HNSCC细胞系中的细胞生长、侵袭和迁移。在本文中,我们主要综述了FAK在HNSCC发生、发展和转移中的研究进展,并提出了HNSCC治疗靶点的前景。