Abstract
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.
Highlights
Breast cancer is still the most prevalent cancer among woman worldwide, approximately one in eight women will develop breast cancer during their life [1]
As a highly heterogeneous disease, breast cancer has been classified into five subtypes based on the histological and molecular characteristics: triplenegative, human epidermal growth factor receptor 2 (HER2)-enriched, luminal B-like HER2 positive, luminal B-like HER2 negative, and luminal A-like [2,3]
There are some treatments that can prolong survival and control treatment-associated toxicity, almost all the patients with metastatic breast cancer will die in 2-3 years [3]
Summary
Breast cancer is still the most prevalent cancer among woman worldwide, approximately one in eight women will develop breast cancer during their life [1]. As a highly heterogeneous disease, breast cancer has been classified into five subtypes based on the histological and molecular characteristics: triplenegative, human epidermal growth factor receptor 2 (HER2)-enriched, luminal B-like HER2 positive, luminal B-like HER2 negative, and luminal A-like [2,3]. Triple negative breast cancer (TNBC), which lacks estrogen receptor (ER), progesterone receptor (PR) and HER2 expression, are the most metastatic and challenging subtype of breast cancer to treat. There are some treatments that can prolong survival and control treatment-associated toxicity, almost all the patients with metastatic breast cancer will die in 2-3 years [3].
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