Diagnostic & targeting reagents for lung cancer

肺癌是美国男性和女性的最大癌症杀手。发现的对象 肺癌细胞表面受体(S)的特异性配体将影响临床问题，包括 功能诊断和细胞特异性药物输送。我们的总体目标是生成一组细胞- 可以用来对肿瘤类型进行分类，然后用于靶向的特定分子 治疗药物的传递。利用噬菌体展示技术，我的实验室开发了平台 分离与特定细胞结合并介导其摄取的多肽的方法。我们有 成功识别了30种不同细胞类型的细胞特异性靶向多肽，包括7种癌细胞 台词。分离的多肽显示出显著的细胞特异性，即使在相似的细胞中也是如此，并且能够 区分正常细胞和癌细胞以及不同的肺肿瘤细胞。这么高 鉴别力表明，可以识别出选择性结合不同肿瘤的多肽 类型，即使是那些具有类似分类的类型。我们建议分离出16个细胞靶向多肽 不同的肺癌株，然后利用这些肽作为诊断和肿瘤特异性递送 试剂。这些多肽将被检测亲和力和细胞特异性。努力的方向将是 将靶向噬菌体转化为小分子靶向试剂，这些多肽支架将 可用于在体外和体内向肿瘤细胞输送治疗药物。细胞特异性 这些多肽表明，它们正在识别不同的细胞表面受体 可能作为肺癌的生物标志物具有临床价值。因此，我们将利用这些多肽来鉴定 这些独特的细胞功能。然后我们将探索该受体在一种 对人肺癌组织进行免疫组织化学染色，并与其表达进行比较 在匹配的正常组织中的水平。实现我们的目标将影响肺癌的诊断和治疗 以及解决靶向药物输送领域的普遍挑战。

Lung cancer is the largest cancer killer of both men and women in the United States. Discoveryof ligands specific to receptor(s) on a surface of a lung cancer cell will impact clinical issues including functional diagnosis andcell-specific drug delivery. Our overall goal is to generate a panel of cell- specific molecules that couldbe used to classify tumor types and then be exploited for targeted delivery of therapeutics. Using phage display technologies, my laboratory has developed platform methodologies to isolate peptides that bind to and mediate uptake into specific cells. We have successfully identified cell-specific targeting peptides for 30 different cell types, including 7 cancer cell lines. The isolated peptides display remarkable cell-specificities, even among similar cells, and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. This high discriminating power suggests that peptides could be identified that selectively bind to differenttumor types, even those with similar classifications. We propose to isolate cell-targeting peptides for 16 different lung cancer lines and then utilize these peptides as diagnostic and tumor specific delivery reagents. These peptides will be assayed for affinity and cell-specificity. Efforts will be directed towards translating the targeting phage into small molecule targeting reagents and these peptide scaffoldswill be utilized to deliver therapeutics to tumor cells both in vitro and in vivo. The cell specificity demonstrated by these peptides indicates that they are recognizing distinct cell surface receptors that may be of clinical value as biomarkers for lung cancer. Thus, we will utilize the peptides to identify the cellular these unique cellular features. We will then explore the expression patterns of the receptor on a panel of human lung cancer tissues by immunohistochemistry and compare this with the expression level in matched normal tissues. Achieving our goals will impact lung cancer diagnosis and treatment as well as solving general challenges in the field of targeted drug delivery.