Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies.
3rd Orthopaedic and Traumatologic Clinic Prevalently Oncologic, IRCCS Istituto Ortopedico, Bologna, Italy.
Curr Opin Oncol. 2022 Jul 1;34(4):322-327. doi: 10.1097/CCO.0000000000000853.
Diffuse-type tenosynovial giant cell tumor (dt-TGCT) is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic, require multiple surgical procedures during their lifetime, and have reduced quality of life (QoL). Surgery is the main treatment with relapse rates ranging from 14 to 55%. The treatment strategy for patients with dt-TGCT is evolving. The purpose of this review is to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of dt-TGCT as well as related therapeutic implications.
TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumor, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as pexidatinib, imatinib, nilotinib, DCC-3014 (vimseltinib), and the monoclonal antibody RG7155 (emactuzumab).
In conclusion, D-TGCT impairs patients' QoL. The evidence that the pathogenetic loop of D-TGCT can be inhibited has changed the therapeutic armamentarium for this condition. Clinical trials of agents that target CSF1R are currently ongoing. All this new evidence should be taken into consideration within multidisciplinary management.
弥漫型腱鞘巨细胞瘤（dt-TGCT）是一种起源于滑膜的良性克隆性肿瘤性增生。患者常出现症状，在其一生中需要多次手术，生活质量（QoL）降低。手术是主要治疗方法，复发率为 14%至 55%。dt-TGCT 患者的治疗策略正在不断发展。本文旨在描述当前的治疗选择，并强调 dt-TGCT 分子发病机制的最新知识以及相关的治疗意义。
TGCT 细胞过度表达集落刺激因子 1（CSF1），导致表达 CSF1 受体（CSF1R）的巨噬细胞募集，这些巨噬细胞是多克隆的，构成了肿瘤的大部分，这导致了 CSF1R 抑制剂的临床试验。这些抑制剂包括小分子如培西达替尼、伊马替尼、尼罗替尼、DCC-3014（vimseltinib）和单克隆抗体 RG7155（emactuzumab）。
总之，dt-TGCT 会降低患者的生活质量。dt-TGCT 发病机制环可以被抑制的证据改变了这种疾病的治疗手段。目前正在进行针对 CSF1R 的药物的临床试验。所有这些新的证据都应该在多学科管理中考虑在内。
