德国海德堡大学Thomas Schmidt和德国欧洲分子生物学实验室Alba Diz-Muñoz研究组合作取得新进展。他们发现降低肝脏转移灶硬度可改善贝伐单抗在转移性结直肠癌中的应答。相关论文发表在2020年6月8日出版的《癌细胞》杂志上。

使用患者样本和原子力显微镜，研究人员发现肝脏转移灶中的组织硬度高于原发性结肠直肠肿瘤。 高度激活的与转移相关的成纤维细胞可增加组织硬度，从而增强血管生成和抗血管生成治疗的抵抗力。

针对肾素-血管紧张素系统的药物通常用于治疗高血压，可抑制成纤维细胞收缩和细胞外基质沉积，从而减少肝转移瘤变硬，并增加贝伐单抗的抗血管生成作用。用贝伐单抗治疗的患者与肾素-血管紧张素抑制剂同时治疗显示出延长的生存期，突出了调节机械微环境对治疗方案的重要性。

附：英文原文

Title: Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer

Author: Ying Shen, Xiaohong Wang, Junyan Lu, Martin Salfenmoser, Naita Maren Wirsik, Nikolai Schleussner, Andrea Imle, Aida Freire Valls, Praveen Radhakrishnan, Jie Liang, Guoliang Wang, Thomas Muley, Martin Schneider, Carmen Ruiz de Almodovar, Alba Diz-Muoz, Thomas Schmidt

Issue&Volume: 2020/06/08

Abstract: Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances angiogenesis and anti-angiogenic therapy resistance. Drugs targeting the renin-angiotensin system, normally prescribed to treat hypertension, inhibit fibroblast contraction and extracellular matrix deposition, thereby reducing liver metastases stiffening and increasing the anti-angiogenic effects of bevacizumab. Patients treated with bevacizumab showed prolonged survival when concomitantly treated with renin-angiotensin inhibitors, highlighting the importance of modulating the mechanical microenvironment for therapeutic regimens.

DOI: 10.1016/j.ccell.2020.05.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30255-5