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）：浆液性卵巢癌是最常见且最具侵袭性的卵巢癌形式。 I期卵巢癌的5年生存率>90%；然而，I 期肿瘤（即局限于卵巢）通常是例外，而不是规则。相反，大多数女性 (~75%) 患有广泛播散性（III/IV 期）疾病，其 5 年生存率仅为 30% 或更低。不幸的是，这个统计数据三十多年来没有改变。此外，虽然大多数患者最初对标准化疗有反应，但大多数患者最终会因化疗耐药性疾病而复发。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检测；然而，两者都不完全具体，并且都可能导致假阳性结果。事实上，目前 FDA 还没有批准用于卵巢癌早期筛查的血清标记物。相反，FDA 批准的 2 个血清生物标志物 CA125 和 HE4 仅在临床上批准用于确定治疗反应和检测疾病复发。我们最近报道了一种新的蛋白质，Elafin，是由卵巢肿瘤细胞合成和分泌的，并且在浆液性卵巢癌亚群中高表达。重要的是，与 CA125 和 HE4 不同，表达 Elafin 的肿瘤患者的总体生存率较差。此外，一种非常具有侵袭性的乳腺癌（称为基底样癌）也表达 Elafin 蛋白，这种乳腺癌更常见于年轻的绝经前女性，包括 BRCA1 突变携带者，而在这些女性中，乳房 X 光检查效果不佳。鉴于弹性蛋白是由这些侵袭性肿瘤分泌的，开发一种测试来检测血液中的弹性蛋白将有助于临床医生对患者进行分类适当的护理和治疗有可能改善发病率和结果。因此，该提案的目标是：1）全面检查Elafin在卵巢癌和乳腺癌中的表达，包括每种疾病的所有亚型以及良性病变，以确定Elafin表达是否真正独特且针对浆液性癌和基底样癌，以及 2) 开发一种基于抗体的测试来检测癌症患者血液中的 Elafin。 Elafin 在乳腺癌和卵巢癌中的表征以及 Elafin 血液检测的开发可能会显着影响患有这些癌症的女性的临床治疗、她们的生存和结果。