PDF(Pubmed)
Abstract：
Taxanes, particularly docetaxel (DTX), has been widely used for combination therapy of head and neck squamous cell carcinoma (HNSCC). For locally advanced unresectable HNSCC, DTX combined with cisplatin and 5-fluorouracil as a revolutionary treatment revealed an advantage in the improvement of patient outcome. In addition, DTX plus immune check inhibitors (ICIs) showed low toxicity and an increased response of patients with recurrent or metastatic HNSCC (R/M HNSCC). Accumulated data indicate that taxanes not only function as antimitotics but also impair diverse oncogenic signalings, including angiogenesis, inflammatory response, ROS production, and apoptosis induction. However, despite an initial response, the development of resistance remains a major obstacle to treatment response. Taxane resistance could result from intrinsic mechanisms, such as enhanced DNA/RNA damage repair, increased drug efflux, and apoptosis inhibition, and extrinsic effects, such as angiogenesis and interactions between tumor cells and immune cells. This review provides an overview of taxanes therapy applied in different stages of HNSCC and describe the mechanisms of taxane resistance in HNSCC. Through a detailed understanding, the mechanisms of resistance may help in developing the potential therapeutic methods and the effective combination strategies to overcome drug resistance.
摘要：
Taxanes,特别是多西他赛（DTX），已广泛用于头颈部鳞状细胞癌（HNSCC）的联合治疗。对于本地高级不可切除的HNSCC，DTX联合顺铂和5-氟尿嘧啶作为革命性的治疗方法，在改善患者预后方面具有优势。此外,DTX加免疫检查抑制剂（ICIs）显示低毒性，复发性或转移性HNSCC（R/MHNSCC）患者的反应增加。积累的数据表明，紫杉烷不仅具有抗有丝分裂药的作用，而且还损害了各种致癌信号。包括血管生成,炎症反应，ROS生产，和凋亡诱导。然而,尽管有最初的反应，耐药性的发展仍然是治疗反应的主要障碍。紫杉烷抗性可能来自内在机制，如增强DNA/RNA损伤修复，增加药物外排，和细胞凋亡抑制，和外在效应，如血管生成和肿瘤细胞与免疫细胞之间的相互作用。本文综述了紫杉烷类药物在HNSCC不同阶段的应用，并描述了紫杉烷类药物在HNSCC中的耐药机制。通过详细的了解,耐药机制可能有助于开发潜在的治疗方法和有效的组合策略来克服耐药。
