NOVEL GENES FOR THE DIAGNOSIS/PROGNOSIS OF BREAST CANCER

本文讨论了利用新型乳腺癌标志物进行实时荧光定量PCR检测的评价和发展，以用于人类乳腺癌的诊断和预后。在美国，乳腺癌是仅次于肺癌的第二大女性死亡原因。良好的预后取决于疾病的早期发现。然而，目前可用的诊断标记的敏感性和特异性是不够的。利用先进的技术、差异显示PCR、cDNA文库和PCR减法，我们鉴定了5种新的乳腺癌标志物，并利用Real - time PCR技术确定了它们在微转移中的组织特异性和潜在存在性。这些新基因将被进一步单独和/或联合评估，以确定用于实时PCR检测微转移的最佳基因组合，并提供更好的乳腺癌诊断/预后。Corixa已经在不同阶段的肿瘤和微转移中实现了这些基因的实时PCR，并将扩大和开发标准化的检测方法。结合与乳腺癌领域主要研究人员的合作以及广泛的血液和组织库的使用，应该能够实现本提案的目标。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检测的商业化。这种测试将在美国和世界范围内销售。这种检测的全球市场估计为每年2 -3亿美元。

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.