NOVEL GENES FOR THE DIAGNOSIS/PROGNOSIS OF BREAST CANCER

该提案讨论了使用新的乳腺癌标志物进行人乳腺癌诊断和预后的真实的时间PCR检测的评价和开发。在美国，乳腺癌是仅次于肺癌的女性死亡率第二高的疾病。良好的预后取决于对这种疾病的早期发现。然而，目前可用的诊断标志物的灵敏度和特异性是不够的。利用改进的最先进的技术，差异显示PCR和cDNA文库和PCR消减方法，我们已经确定了5个新的乳腺癌标志物，并建立了它们的组织特异性和潜在的存在微转移使用真实的时间PCR。这些新基因将单独和/或组合进行进一步评估，以确定用于真实的实时PCR测定的基因的最佳组合，以检测微转移并提供乳腺癌的改善的诊断/预后。在Corixa已经实现了对不同阶段肿瘤和微转移的这些基因的真实的时间PCR，并且将扩展和开发标准化测定。这一点，加上与乳腺癌领域的主要研究人员的合作，以及获得广泛的血液和组织库，应能使本提案的目标和目的得以实现。拟定商业应用：拟议的研究将导致商业化的高通量RT-PCR检测乳腺癌的诊断和/或预后。这种测试将在美国和世界范围内销售。这种测试的全球市场估计为2亿至3亿美元/年。

This proposal discusses the evaluation and development Real time PCR assays using novel breast cancer markers for the diagnosis and prognosis of human breast cancer. Breast cancer is second only to lung cancer in deaths among women in the U.S. Good prognosis depends on the early detection of the disease. However, the sensitivity and the specificity of the current available diagnostic markers is not sufficient. Using improved state of the art technology, differential display PCR and cDNA library and PCR subtraction methods, we have identified 5 novel breast cancer markers and established their tissue specificity and potential presence in micrometastases using Real time PCR. These novel genes will be further evaluated alone and/or in combination to determine the optimal combination of genes for use in Real time PCR assays to detect micrometastases and provide improved diagnosis/prognosis of breast cancer. Real time PCR with these genes on different stage tumors and micrometastases has already been achieved at Corixa and will be expanded and standardized assays developed. This in combination with collaborations with key investigators in the area of breast cancer and access to an extensive blood and tissue bank should enable the goals and objectives of this proposal to be achieved. PROPOSED COMMERCIAL APPLICATION: The proposed studies will lead to commercialization of a high throughput RT-PCR assay for diagnosis and /or prognosis of breast cancer. Such tests would be marketed both in the U.S. and worldwide. The estimated world wide market for such a tests is $200-300 million/year.