Liu Sijia, Ten Dijke Peter
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Oncode Institute, Leiden University Medical Center, Leiden, Netherlands.
Oncoscience. 2020 Nov 9;7(11-12):85-87. doi: 10.18632/oncoscience.518. eCollection 2020 Nov.
Breast cancer is a highly heterogeneous disease with dynamic changes in the tumor microenvironment. Precision medicine will in the future provide the possibility to treat each individual cancer patient with the right (combination) therapy specifically tailored to personal needs. However, in order to accomplish this, more accurate biomarkers for precise diagnosis, prognosis, therapy response, and target-specific drugs are required. Although an increasing number of (epi)genetic driving alterations have been reported in breast cancer, the major stumbling block for clinical application of many of them is that they are difficult to therapeutically target. Deubiquitinases (DUBs) are emerging drug targets that play important roles in cancer progression. Hence, we devoted our efforts to uncover the global DUB activity landscape of breast cancer in order to discover potential novel biomarkers or therapeutic targets. We developed a specific DUB activity-based inhibitor and probe and applied it to obtain new insights into breast cancer.
乳腺癌是一种高度异质性疾病，其肿瘤微环境存在动态变化。精准医学未来将为针对每个癌症患者的个人需求量身定制合适的（联合）治疗方案提供可能。然而，要实现这一点，需要更准确的生物标志物用于精确诊断、预后评估、治疗反应监测以及靶向特异性药物。尽管在乳腺癌中已报道了越来越多的（表观）遗传驱动改变，但其中许多改变在临床应用中的主要障碍是它们难以成为治疗靶点。去泛素化酶（DUBs）是新兴的药物靶点，在癌症进展中发挥重要作用。因此，我们致力于揭示乳腺癌的整体DUB活性图谱，以发现潜在的新型生物标志物或治疗靶点。我们开发了一种基于DUB活性的特异性抑制剂和探针，并将其应用于深入了解乳腺癌。
