Kischel Philippe, Waltregny David, Castronovo Vincent
Belgian National Fund for Scientific Research, University of Liège, Metastasis Research Laboratory, Center for Experimental Cancer Research, Bât. B23, CHU Sart-Tilman Liège, B-4000 Liège, Belgium.
Expert Rev Proteomics. 2007 Dec;4(6):727-39. doi: 10.1586/14789450.4.6.727.
One promising avenue towards the development of more selective, better anticancer drugs lies in the targeted delivery of bioactive compounds to the tumor environment by means of binding molecules specific for tumor-associated biomarkers. Eligibility of such markers for therapeutic ideally use three criteria: accessibility from the bloodstream; expression at sufficient level, and no (or much lower) expression in normal tissues. Most current discovery strategies (such as biomarker searching into body fluids) provide no clue as to whether proteins of interest are accessible, in human tissues, to suitable high-affinity ligands, such as systemically delivered monoclonal antibodies. To address this limitation, our group recently developed two methodologies based on chemical proteomic modifications, enabling the discovery of proteins accessible from the bloodstream and the extracellular space in human pathological tissues. In this review, we will discuss the potential benefits of these methodologies for the fast discovery of therapeutically valuable biomarkers.
开发更具选择性、更好的抗癌药物的一个有前景的途径是通过对肿瘤相关生物标志物具有特异性的结合分子将生物活性化合物靶向递送至肿瘤环境。此类标志物用于治疗的理想条件有三条标准：可从血液中获取；有足够水平的表达，且在正常组织中无（或低得多）表达。目前大多数发现策略（如在体液中搜索生物标志物）无法提供关于感兴趣的蛋白质在人体组织中是否可被合适的高亲和力配体（如全身递送的单克隆抗体）所获取的线索。为解决这一局限性，我们团队最近开发了两种基于化学蛋白质组修饰的方法，能够发现人体病理组织中可从血液和细胞外空间获取的蛋白质。在本综述中，我们将讨论这些方法对于快速发现具有治疗价值的生物标志物的潜在益处。
