Kallikrein-related serine proteases as therapeutic targets for cancer

异常的蛋白质水解与许多疾病有关，包括癌症。许多制药公司已经将蛋白酶作为开发癌症和其他疾病新疗法的目标。我们的实验室正在领导一项与丝氨酸蛋白酶家族有关的研究，该家族被称为“人体组织钾化酶”（KLKs）。这些klk是15种细胞外蛋白酶，似乎与肿瘤进展密切相关。因此，我们相信klk代表了一个新的、有希望的癌症药物靶点。在这个应用中，我们建议临床前验证小肽激酶家族的一些成员作为治疗癌症的治疗靶点。我们将使用定量蛋白质组学，体外细胞检测和动物异种移植模型来增加我们对乳腺癌中钾化激酶病理生理的理解。这项研究可能会导致乳腺癌和其他癌症的新疗法的发展。

Aberrant proteolysis is associated with many diseases, including cancer. Already, many Pharmaceutical companies are targeting proteases for developing new therapeutics for cancer and other diseases. Our laboratory is leading research related to a family of serine proteases called "human tissue kallikreins" (KLKs). These KLKs are 15 extracellular proteases which appear to be closely linked to tumour progression. We thus believe that KLKs represent a new, and promising, cancer drug target. In this application, we propose to pre-clinically validate a few members of the kallikrein family as therapeutic targets for treatment of cancer. We will use quantitative proteomics, in-vitro cell-based assays and animal xenograft models to increase our understanding of kallikrein pathophysiology in breast cancer. This investigation may lead to development of novel therapies for breast and other cancers.