NOVEL GENES FOR THE DIAGNOSIS/PROGNOSIS OF BREAST CANCER

这项建议讨论了使用新的乳腺癌标志物的实时荧光定量聚合酶链式反应技术在乳腺癌诊断和预后中的评价和发展。在美国女性死亡人数中，乳腺癌仅次于肺癌。良好的预后取决于这种疾病的早期发现。然而，目前可用的诊断标记物的敏感性和特异性是不够的。利用改进的技术、差异显示技术、文库技术和差减技术，我们鉴定了5个新的乳腺癌标记物，并利用实时定量聚合酶链式反应确定了它们的组织特异性和在微转移中的潜在存在。这些新基因将进一步单独和/或联合进行评估，以确定用于实时荧光聚合酶链式反应检测微转移并改善乳腺癌诊断/预后的最佳基因组合。Corixa已经在不同阶段的肿瘤和微转移上实现了这些基因的实时聚合酶链式反应，并将扩大和发展标准化的检测方法。这一点，再加上与乳腺癌领域的关键研究人员的合作，以及获得广泛的血液和组织库，应该能够实现这项提案的目标和目的。拟议的商业应用：拟议的研究将导致用于乳腺癌诊断和/或预后的高通量RT-PCR分析的商业化。这样的测试将在美国和世界范围内销售。据估计，这种测试的全球市场规模为2-3亿美元/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.