Molecular Targets - Colon Cancer

我们正在使用一种新的策略来确定治疗和预防常见癌症的分子靶点，最初的重点是结肠癌。该战略利用数据挖掘基因组信息，通过NCI癌症基因组解剖项目（CGAP）生成并提供给公众，并将这些信息与实验方法相结合。使用CGAP提供的与LPG联合开发的工具，我们查询了CGAP数据库，发现665个序列（基因、est和SAGE标签）在结肠癌文库中表达，而在正常必需组织文库中没有表达。其中，356个在Affytron HGU 95 A-E芯片上，因此成为我们选择的实验平台。从16个正常的必需组织中获得的mRNA在Affytron表达阵列上进行了测定，发现通过数据挖掘鉴定的并存在于芯片上的242个序列在所有测定的正常组织中是沉默的。接下来，我们分析了来自结肠癌样本的RNA，并鉴定了至少一个结肠癌样本中表达的22个（22/242）序列。虽然这22个序列的作用目前尚不清楚，但我们预计，用于界定不在重要器官中表达的靶点的初始投资将促进开发有效、无毒的癌症治疗药物。 除了确定药物开发的目标之外，很明显，这些目标也可以用于药物递送，作为疾病的早期分子标志物，或作为药物递送和药物有效性的替代标志物。因此，这种一般的，系统的策略应该是有用的，在确定目标的预防和检测许多常见的癌症。

We are using a novel strategy to identify molecular targets for the therapy and prevention of common cancers, with an initial focus on colon cancer. The strategy capitalizes on data mining genomic information, generated and made available to the public through the NCI Cancer Genome Anatomy Project (CGAP), and combines this information with an experimental approach. Using tools provided by CGAP and developed in association with the LPG, we queried the CGAP database and found 665 sequences (genes, est's, and SAGE tags) expressed in colon cancer libraries and not in libraries from normal essential tissues. Of these, 356 are present on the Affymetrix HGU95 A-E chips, and thus became our experimental platform of choice. mRNA obtained from 16 normal essential tissues was assayed on the Affymetrix expression arrays and 242 of the sequences identified through data mining and present on the chips were found to be silent in all normal tissues assayed. We next assayed the RNA from colon cancer samples and identified 22 (22/242) sequences that were expressed in at least one of the colon cancer samples. Although the role of these 22 sequences is unknown at present, we anticipate that the initial investment spent delimiting targets not expressed in essential organs will facilitate the development of effective, non-toxic agents for cancer treatment. In addition to identifying targets of interest for drug development, it is clear that such targets could also be exploited for drug delivery, as early molecular markers of disease, or as surrogate markers for drug delivery and drug effectiveness. Thus, this general, systematic strategy should be useful in the identification of targets for the prevention and detection of many common cancers.