A SYSTEMATIC APPROACH TO EARLY DIAGNOSIS OF CANCER

成功治疗癌症的一个无可争议的关键是早期诊断。这有力地证明了参与常规筛查计划的必要性。然而，那些已经到位的系统目前都存在明显的缺陷。未来几年应用癌症研究的一个主要推动力将是寻找改进的诊断方法。设计新的监测方法的一个途径是识别肿瘤细胞的特征标记。这项研究的基础有两个方面。我们将使用Genetica陷阱技术筛选从结肠癌、乳腺癌和前列腺癌中制备的文库，以寻找编码转运蛋白的基因。此后，我们将使用“现成的”技术来评估这些基因在正常细胞和肿瘤细胞中的差异表达。这些研究将导致建立肿瘤特异性基因文库，这些基因编码分泌蛋白和细胞表面蛋白。这些将用于产生免疫试剂来分析血液和细胞表面标记物，以确定诊断早期肿瘤的蛋白质。拟议的商业应用：拟议的研究有许多商业应用。主要是鉴定血源性、肿瘤特异性蛋白质，可用于常规诊断测试的开发。此外，我们可以确定肿瘤显像剂的潜在靶点。最后，肿瘤特异性受体可能为小分子抗肿瘤药物或生物治疗药物的开发提供起点。

One of the undisputed keys to the successful treatment of cancer is early diagnosis. This strongly argues for participation in routine screening programs. However, those that are in place currently suffer from significant drawbacks. A major thrust of applied cancer research in the coming years will be a search for improved diagnostic methodologies. One route toward the design of new surveillance methods is the identification of markers that are characteristic of tumor cells. The foundation of the proposed research is two-fold. We will use the Genetica trap technology to sift libraries prepared from colon, breast and prostate carcinomas for genes encoding trafficked proteins. Thereafter, we will use "off-the-shelf"technologies to assess differential expression of such genes in normal and tumor cells. These studies will lead to the creation of libraries of tumor-specific genes that encode secreted and cell surface proteins. These will be used to generate immunological reagents to analyze blood born and cell surface markers in order to identify proteins that are diagnostic of early stage tumors. PROPOSED COMMERCIAL APPLICATIONS: There are a multitude of commercial applications for the proposed research. Primary is the identification of blood-borne, tumor specific proteins that can be used for the development of routine diagnostic tests. In addition, we may identify potential targets for tumor imaging agents. Finally, tumor-specific receptors may be provide starting points for the development of small-molecule anti-tumor drugs or biotherapeutics.