Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia.
Department of Surgery, The University of Melbourne, Melbourne, VIC, Australia.
Target Oncol. 2022 May;17(3):223-252. doi: 10.1007/s11523-022-00876-z. Epub 2022 Apr 21.
Sporadic desmoid-type fibromatosis is a rare, fibroblastic soft-tissue neoplasm with local aggressiveness but no metastatic potential. Aberrant Wnt/β-catenin signalling has been extensively linked to desmoid pathogenesis, although little is known about other molecular drivers and no established treatment approach exists. We aimed to summarise the current literature regarding the molecular pathogenesis of sporadic desmoid-type fibromatosis and to discuss the effects of both current and emerging novel therapies targeting these mechanisms. A literature search was conducted of MEDLINE ALL and EMBASE databases for published studies (2000-August 2021) using keywords related to 'fibromatosis aggressive', 'immunohistochemistry', 'polymerase chain reaction' and 'mutation'. Articles were included if they examined the role of proteins in sporadic or extra-abdominal human desmoid-type fibromatosis pathogenesis. Searching identified 1684 articles. Following duplicate removal and eligibility screening, 36 were identified. After a full-text screen, 22 were included in the final review. At least 47% of desmoid-type fibromatosis cases displayed aberrant β-catenin immunoreactivity amongst ten studies. Cyclin D1 overexpression occurred in at least 40% of cases across five studies. Six studies reported oestrogen receptor-β expression with a range of 7.4-90%. Three studies implicated matrix metalloproteinases, with one study demonstrating vascular endothelial growth factor overexpression. One study explored the positive relationship between cyclooxygenase-2 and platelet-derived growth factor receptor-β. Aberrant Wnt/β-catenin signalling is a well-established pathogenic driver that may be targeted via downstream modulation. Growth factor signalling is best appreciated through the clinical trial effects of multi-targeted tyrosine kinase inhibitors, whilst oestrogen receptor expression data may only offer a superficial insight into oestrogen signalling. Finally, the tumour microenvironment presents multiple potential novel therapeutic targets.
散发性韧带样型纤维瘤病是一种罕见的成纤维细胞性软组织肿瘤，具有局部侵袭性，但无转移潜能。异常的 Wnt/β-连环蛋白信号通路与韧带样型纤维瘤病的发病机制密切相关，尽管人们对其他分子驱动因素知之甚少，也没有确立的治疗方法。我们旨在总结散发性韧带样型纤维瘤病的分子发病机制的现有文献，并讨论针对这些机制的当前和新兴新型治疗方法的效果。我们对 MEDLINE ALL 和 EMBASE 数据库进行了文献检索，使用了与“纤维瘤病侵袭性”、“免疫组织化学”、“聚合酶链反应”和“突变”相关的关键词，以搜索 2000 年 8 月至 2021 年 8 月期间发表的研究文献。如果文章检查了蛋白质在散发性或腹外韧带样型纤维瘤病发病机制中的作用，则将其纳入。搜索共确定了 1684 篇文章。经过重复去除和资格筛选，确定了 36 篇。经过全文筛选，最终有 22 篇文章纳入综述。在 10 项研究中，至少有 47%的韧带样型纤维瘤病病例显示异常的β-连环蛋白免疫反应性。在 5 项研究中，至少有 40%的病例 cyclin D1 过表达。有 6 项研究报道了雌激素受体-β的表达，范围为 7.4-90%。有 3 项研究涉及基质金属蛋白酶，其中 1 项研究表明血管内皮生长因子过表达。有 1 项研究探讨了环加氧酶-2 与血小板衍生生长因子受体-β之间的正相关关系。异常的 Wnt/β-连环蛋白信号通路是一种已确立的致病驱动因素，可通过下游调节来靶向。生长因子信号通路最好通过多靶点酪氨酸激酶抑制剂的临床试验效果来评估，而雌激素受体表达数据可能只是对雌激素信号的表面了解。最后，肿瘤微环境提供了多个潜在的新的治疗靶点。
