Elafin as a biomarker in serous ovarian cancers and basal-like breast tumors

Elafin 作为浆液性卵巢癌和基底样乳腺肿瘤的生物标志物

基本信息

批准号：
8445879
负责人：
Ronny I DRAPKIN
金额：
$ 22.45万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-11 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8445879
关键词：
Address Adnexal Mass Affect Aftercare Age American Antibodies BRCA1 Mutation Benign Biological Assay Biological Markers Blood Circulation Blood Tests Breast Breast Cancer Cell Breast Carcinoma CA-125 Antigen Cancer Patient Cancer cell line Carcinoma Caring Cell Line Cessation of life Clear Cell Clinical Clinical Management Collection Cystadenoma Data Detection Development Diagnosis Diagnostic Disease Disease Resistance Early Diagnosis Epididymis Epithelium Evaluation FDA approved Female Fibroadenoma Gene Cluster Gene Expression Gene Expression Profiling Genes Goals Human Human Chromosomes Immunohistochemistry Incidence Individual Laboratories Lead Lesion Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Mammary Gland Parenchyma Mammary Neoplasms Mammography Mass Spectrum Analysis Measures Mitogen-Activated Protein Kinases Modality Molecular Molecular Profiling Morbidity - disease rate Mucinous Myoepithelial cell Outcome Ovarian Ovarian Carcinoma Ovarian Serous Adenocarcinoma Ovary PI3 gene Pathway interactions Patient Monitoring Patients Premenopause Proteins Recurrence Relapse Reporting Role Sampling Screening for Ovarian Cancer Serous Serum Serum Markers Sex Cord-Gonadal Stromal Tumors Specimen Staging Subgroup Survival Rate Testing Transvaginal Ultrasound Triage WFDC2 gene Woman Work base cancer cell chemotherapy endometriosis improved malignant breast neoplasm member molecular phenotype mortality mutation carrier neoplastic cell novel ovarian neoplasm overexpression programs public health relevance response screening statistics tool tumor young woman

项目摘要

DESCRIPTION (provided by applicant): Serous ovarian carcinoma is the most common and aggressive form of ovarian cancer. The 5 year survival rate for stage I ovarian cancer is >90%; however, stage I tumors (i.e., confined to the ovary) are more often the exception than the rule. Instead, most women (~75%) present with widely disseminated (stage III/IV) disease, for which the 5 year survival rate is a dismal 30% or less. Unfortunately, this statistic has not changed in over 3 decades. Furthermore, while most patients initially respond to standard chemotherapy, the majority ultimately relapse with chemo-resistant disease. The best tools available for detecting early-stage disease are transvaginal ultrasound and serum biomarker testing; however, neither is entirely specific and both can lead to false-positive results. In fact, no seru markers are currently FDA approved for early screening for ovarian cancer. Instead the 2 FDA approved serum biomarkers, CA125 and HE4, are only approved clinically for determining response to treatment and for detecting recurrence of disease. We recently reported that a novel protein, Elafin, is synthesized and secreted by ovarian tumor cells, and is highly expressed in subset of serous ovarian carcinomas. Importantly, unlike CA125 and HE4, patients whose tumors express Elafin have a poor overall survival. In addition, the Elafin protein is also expressed by a very aggressive form of breast cancer, called basal-like carcinoma, which occurs more frequently in younger, pre-menopausal women, including BRCA1 mutation carriers, where mammography is not as effective. Given that Elafin is secreted by these aggressive tumors, developing a test to detect it in the bloodstream would help clinicians triage patients for appropriate care and treatment, having the potential to improve morbidity and outcome. Therefore, the goals of this proposal are: 1) comprehensively examine Elafin expression in ovarian and breast cancers, including all subtypes of each disease as well as benign lesions, to determine whether Elafin expression is truly unique and specific to serous and basal-like carcinomas, and 2) to develop an antibody-based test to detect Elafin in the bloodstream of cancer patients. Characterization of Elafin in breast and ovarian cancers and the development of an Elafin blood test may significantly impact the clinical management of women with these cancers, their survival, and outcome.

描述（由申请人提供）：浆液卵巢癌是卵巢癌最常见和最具侵略性的形式。 I期卵巢癌的5年生存率> 90％；但是，I期肿瘤（即局限于卵巢）比规则更常见。取而代之的是，大多数女性（约75％）出现了广泛传播的（III/IV期）疾病，为此，5年生存率为30％或更少。不幸的是，这种统计数据在三十多年来没有改变。此外，尽管大多数患者最初对标准化疗反应，但大多数患者最终会因化学抗性疾病而复发。可用于检测早期疾病的最佳工具是经阴道超声和血清生物标志物测试。但是，这两个都不是完全具体的，两者都可以导致假阳性结果。实际上，目前尚无FDA批准SERU标记来进行卵巢癌的早期筛查。取而代之的是，2 FDA批准的血清生物标志物CA125和HE4仅在临床上批准用于确定对治疗的反应和检测疾病复发。我们最近报道说，一种新型的蛋白质Elafin是由卵巢肿瘤细胞合成和分泌的，并且在浆液卵巢癌的子集中高度表达。重要的是，与CA125和HE4不同，肿瘤表达Elafin的患者总生存率较差。此外，elafin蛋白还以一种非常侵略性的乳腺癌（称为基底样癌）表达，该癌在年轻的绝经前妇女（包括BRCA1突变携带者）中更频繁地发生，其中乳腺X线摄影不那么有效。鉴于Elafin被这些侵略性肿瘤分泌，因此在血液中进行检测的测试将有助于临床医生分类患者适当的护理和治疗，具有改善发病率和结果的潜力。 Therefore, the goals of this proposal are: 1) comprehensively examine Elafin expression in ovarian and breast cancers, including all subtypes of each disease as well as benign lesions, to determine whether Elafin expression is truly unique and specific to serous and basal-like carcinomas, and 2) to develop an antibody-based test to detect Elafin in the bloodstream of cancer patients. Elafin在乳腺癌和卵巢癌中的表征以及Elafin血液测试的发展可能会严重影响女性使用这些癌症的临床管理，其生存和结果。