Tumor Heterogeneity Metastasis and Resistance, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
EMBO Mol Med. 2022 Jun 8;14(6):e14283. doi: 10.15252/emmm.202114283. Epub 2022 May 4.
Breast cancer is the most frequent cancer among women, and metastases in distant organs are the leading cause of the cancer-related deaths. While survival of early-stage breast cancer patients has increased dramatically, the 5-year survival rate of metastatic patients has barely improved in the last 20 years. Metastases can arise up to decades after primary tumor resection, hinting at microenvironmental factors influencing the sudden outgrowth of disseminated tumor cells (DTCs). This review summarizes how the environment of the most common metastatic sites (lung, liver, bone, brain) is influenced by the primary tumor and by the varying dormancy of DTCs, with a special focus on how established metastases persist and grow in distant organs due to feed-forward loops (FFLs). We discuss in detail the importance of FFL of cancer cells with their microenvironment including the secretome, interaction with specialized tissue-specific cells, nutrients/metabolites, and that novel therapies should target not only the cancer cells but also the tumor microenvironment, which are thick as thieves.
乳腺癌是女性最常见的癌症，远处器官转移是癌症相关死亡的主要原因。虽然早期乳腺癌患者的生存率有了显著提高，但在过去 20 年中，转移性患者的 5 年生存率几乎没有改善。转移可以在原发肿瘤切除后长达几十年发生，这表明影响播散性肿瘤细胞（DTC）突然生长的微环境因素。这篇综述总结了常见转移部位（肺、肝、骨、脑）的环境如何受原发肿瘤和 DTC 不同休眠的影响，并特别关注已建立的转移如何由于前馈环（FFL）而在远处器官中持续和生长。我们详细讨论了癌细胞与其微环境（包括分泌组、与专门的组织特异性细胞的相互作用、营养物质/代谢物）的 FFL 的重要性，以及新的治疗方法不仅应该针对癌细胞，还应该针对肿瘤微环境，因为它们是一丘之貉。
