Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide according to GLOBOCAN estimates from 2022. Current therapy options for recurrent or metastatic disease are limited to conventional cytotoxic chemotherapy and immunotherapy, with few targeted therapy options readily available. Recent single-cell transcriptomic analyses identified TGF-β signaling as an important mediator of functional interplays between cancer-associated fibroblasts and a subset of mesenchymal cancer cells. This signaling was shown to drive invasiveness, treatment resistance, and immune evasion. These data provide renewed interest in the TGF-β pathway as an alternative therapeutic target, prompting a critical review of previous clinical data which suggest a lack of benefit from TGF-β inhibitors. While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy.
根据2022年全球癌症统计数据显示，头颈部鳞状细胞癌是全球第六大常见癌症。目前针对复发或转移性头颈部鳞癌的治疗方案主要局限于传统细胞毒性化疗和免疫治疗，可用的靶向治疗选择极为有限。近期单细胞转录组学分析发现，TGF-β信号通路是癌症相关成纤维细胞与间充质型癌细胞亚群之间功能相互作用的重要介质。研究表明该信号通路可驱动肿瘤侵袭性、治疗抵抗和免疫逃逸。这些发现重新激发了将TGF-β通路作为替代治疗靶点的研究兴趣，促使我们对既往临床数据进行批判性评估——这些数据曾提示TGF-β抑制剂缺乏临床获益。虽然临床前研究已证明TGF-β抑制剂具有显著的抗肿瘤潜力，但正在进行和已完成的临床试验结果却不尽如人意，凸显了将这些研究成果转化为临床实践的困难。本专题综述将探讨TGF-β抑制剂在头颈部鳞癌中的相关临床前及临床研究进展，并深入分析患者分层在该治疗策略发展中的潜在作用。
Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma
肿瘤(癌症)患者之家