Development of a novel serum diagnosis for breast cancer

描述(申请人提供)：在美国，每年有20万名女性被诊断出患有乳腺癌，其中4万名女性将死于这种疾病。目前还没有用于筛查乳腺癌患者的血清诊断方法。此外，监测乳腺癌患者治疗反应的可能性有限。迫切需要一种与治疗齐头并进的血清生物测定来诊断和/或监测乳腺癌患者。我们已将PC细胞衍生生长因子(PCDGF/GP88)确定为乳腺癌治疗和诊断发展的分子靶点。生物学和病理学研究已证实PCDGF在乳腺癌中的重要作用。PCDGF在人乳腺癌中高表达。抑制PCDGF表达可抑制裸鼠体内肿瘤生长。PCDGF在80%的浸润性导管癌中高表达，与预后不良的临床参数有关，而正常组织和良性病变均为阴性。A&G制药公司目前正在开发基于抑制PCDGF对乳腺癌细胞作用的治疗方法。最近，A&G制药公司开发了一种检测血清和血浆中循环PCDGF水平的EIA方法。我们已经建立了对照组血清PCDGF水平的基线，并在有限数量的患者中显示，进展性疾病患者的PCDGF水平升高。这个SBIR第一阶段的重点是一项大规模的可行性研究，以确定血清PCDGF检测在乳腺癌患者诊断中的潜力。方法：采用EIA法检测600例乳腺癌患者手术前、术后、治疗后6个月和1年的血清PCDGF水平。110份匹配的对照血清样本也将被分析。数据将进行统计分析，并与临床参数和治疗反应相关联。这项SBIR第一阶段研究将通过建立概念验证为第二阶段的应用奠定基础。到第二阶段计划结束时，A&G预计将完成FDA 510K应用血清PCDGF检测试剂盒用于诊断和/或监测乳腺癌患者所需的所有诊断临床试验。

DESCRIPTION (provided by applicant): Each year 200,000 women in the US are diagnosed with breast cancer, and 40,000 women will die of the disease. Serum diagnosis for screening breast cancer patients is not yet available. Moreover, there is only limited possibility for monitoring response to therapy of breast cancer patients. A serum bioassay that works hand-in-hand with therapy for the diagnosis and/or the monitoring of breast cancer patients is desperately needed. We have identified PC-Cell Derived Growth Factor (PCDGF/GP88) as a molecular target for the development of breast cancer therapy and diagnosis. Biological and pathological studies have demonstrated the critical role of PCDGF in breast carcinoma. PCDGF is overexpressed in human breast carcinoma. Inhibition of PCDGF expression leads to the inhibition of tumor growth in nude mice. PCDGF is overexpressed in 80% of invasive ductal carcinoma in correlation with clinical parameters of poor prognosis whereas normal tissues and benign lesions are negative. Therapy development based on inhibiting PCDGF action on breast cancer cells is currently being developed at A&G Pharmaceutical. Recently, A&G Pharmaceutical has developed an EIA to detect circulating PCDGF level in serum and plasma. We have established a baseline for PCDGF serum level in control individuals, and showed with a limited number of patients that PCDGF level was elevated in patients with progressive disease. This SBIR Phase I focuses on a large-scale feasibility study to determine the potential of serum PCDGF assay for the diagnosis of breast cancer patients. Methods: Circulating PCDGF will be measured by EIA using serum samples from 600 breast cancer patients collected at 4 specific time points: before surgery, after surgery, after 6 months and one year of therapy. 110 matched control serum samples will also be analyzed. Data will be statistically analyzed and correlated to clinical parameters and response to therapy. This SBIR Phase I study will lay the foundation for Phase II application by establishing proof of concept. By the end of Phase II program, A&G expects to complete all diagnostic clinical trials necessary for FDA 510K application for the serum PCDGF determination kit to be used for diagnosis and/or monitoring of breast cancer patients.