Nordic Bioscience, Herlev Hovedgade 205-207, 2730, Herlev, Denmark.
Bristol Myers Squibb, Princeton, NJ, USA.
Cell Mol Life Sci. 2022 Mar 25;79(4):204. doi: 10.1007/s00018-022-04226-0.
Due to activation of fibroblast into cancer-associated fibroblasts, there is often an increased deposition of extracellular matrix and fibrillar collagens, e.g. type III collagen, in the tumor microenvironment (TME) that leads to tumor fibrosis (desmoplasia). Tumor fibrosis is closely associated with treatment response and poor prognosis for patients with solid tumors. To assure that the best possible treatment option is provided for patients, there is medical need for identifying patients with high (or low) fibrotic activity in the TME. Measuring unique collagen fragments such as the pro-peptides released into the bloodstream during fibrillar collagen deposition in the TME can provide a non-invasive measure of the fibrotic activity. Based on data from 8 previously published cohorts, this review provides insight into the prognostic value of quantifying tumor fibrosis by measuring the pro-peptide of type III collagen in serum of a total of 1692 patients with different solid tumor types and discusses the importance of tumor fibrosis for understanding prognosis and for potentially guiding future drug development efforts that aim at overcoming the poor outcome associated with a fibrotic TME.
由于成纤维细胞向癌相关成纤维细胞的激活,肿瘤微环境(TME)中常常会有细胞外基质和纤维胶原(如 III 型胶原)的过度沉积,导致肿瘤纤维化(纤维变性)。肿瘤纤维化与实体瘤患者的治疗反应和预后不良密切相关。为了确保为患者提供最佳的治疗选择,临床上需要确定 TME 中具有高(或低)纤维化活性的患者。测量 TME 中纤维胶原沉积过程中释放到血液中的前肽等独特胶原片段,可以提供一种非侵入性的纤维化活性测量方法。基于之前发表的 8 个队列的数据,本综述通过测量血清中 III 型胶原的前肽,深入了解了定量肿瘤纤维化的预后价值,该研究共纳入了 1692 名不同实体瘤类型的患者,并讨论了肿瘤纤维化对理解预后和潜在指导未来药物开发工作的重要性,这些工作旨在克服与纤维化 TME 相关的不良结局。