A Circulating Biomarker for use in Monitoring Metastatic Breast Cancer

用于监测转移性乳腺癌的循环生物标志物

基本信息

批准号：
10477924
负责人：
Ginette Serrero
金额：
$ 7.08万
依托单位：
A AND G PHARMACEUTICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10477924
关键词：
Applications Grants Biological Biological Markers Biological Process Blood Blood Circulation Blood Tests Blood specimen Breast Cancer Patient Caring Cessation of life Characteristics Clinical Clinical Data Clinical Management Clinical assessments Complement Consumption Data Dependence Diagnostic Diagnostic tests Disease Disease Management Disease Progression Disseminated Malignant Neoplasm Drug resistance Enrollment Enzyme Immunoassay Exposure to Frequencies Future Glycoproteins Gold Growth Health Image Imaging technology Individual Insurance Laboratories Liquid substance Longitudinal Studies Longitudinal prospective study Measurable Measurement Measures Metastatic breast cancer Monitor Neoplasm Circulating Cells Oncologist Outcome PGRN gene Patient Monitoring Patients Pharmaceutical Preparations Phase Population Process Quality of life Radiation Radiation exposure Recurrence Retrospective Studies Retrospective cohort Risk Sampling Scanning Schedule Serum Small Business Innovation Research Grant Stratification Testing Therapeutic Time Toxic effect Tumor Markers Tumor Tissue Work autocrine base cancer cell circulating biomarkers clinical examination clinical research site commercialization cost cost effective experience follow-up improved innovation malignant breast neoplasm minimally invasive novel patient population patient stratification predicting response prospective real time monitoring response standard of care treatment response tumor tumorigenesis

项目摘要

Cost-effective and minimally invasive monitoring of metastatic breast cancer (MBC) patients for disease progression or response to therapy is an unmet need in the clinical management of the disease. Imaging technologies are currently the gold standard of such monitoring. However, there is controversy regarding the type & frequency of imaging required. Imaging is expensive, time consuming, slow to detect disease changes and raises concern about repeated radiation exposure and costs are not always covered by insurance. Complementary approaches to imaging such as circulating tumor cells and biomarkers are used in the Standard of Care (SOC), although their application remains limited. A simple, cost-effective blood test to measure the level of biomarkers which are drivers of the disease aggressiveness should provide novel solutions for real-time monitoring of therapy response and reduce dependency on imaging in the MBC population. The PI has identified an 88kDa glycoprotein GP88 (progranulin), elucidated its biological activity as an autocrine growth & survival factor. GP88 is secreted from cancer cells and measurable in biological fluids at higher levels in breast cancer patients, compared to healthy individuals. Based on these characteristics, an innovative diagnostic test (Enzyme Immunoassay – EIA) to measure GP88 in circulation was established. Our SBIR Phase 1 retrospective study demonstrated a statistical association between serum GP88 levels measured by the EIA test and objective measures of disease, i.e. RECIST 1.1 in 101 MBC patients. We established that a serum GP88 level of 56ng/mL was a stratification point below which patients have improved overall survival while patients with GP88>56 ng/ml have a poor outcome. We showed that serum GP88 levels were statistically correlated to response to therapy in addition to progression of disease unlike the SOC biomarker CA15-3 which is only associated to progression of disease. Based on these promising data, we are proposing an SBIR Phase 2 prospective longitudinal study over a 15-month period enrolling 120 MBC patients at two clinical sites by measuring serum GP88 level every month with imaging performed every 3 months. The objectives are to validate the findings of phase 1 and establish the predictive use of the GP88 test in monitoring MBC patients for disease progression/ response as an adjunct to imaging and aid in the clinical management of such patients. Specifically, we will (1) Validate that serum GP88 levels are correlated to disease response/ progression as defined by imaging results; (2) Examine the impact of successive high (>56ng/mL) and low (<56ng/mL) GP88 blood levels on future response/ progression and time to progression as defined by imaging results; (3) Validate that patients with consistent low (<56ng/mL) GP88 blood levels, have improved survival compared with patients with consistently high (>56ng/mL) GP88 blood levels. The outcomes of this phase 2 will be to establish clinical data to support commercialization of GP88 EIA as an integral part of clinical management of MBC patients that will contribute to improved care of MBC patients at reduced cost.

疾病转移性乳腺癌（MBC）患者的成本效益和微创监测对治疗的进展或反应是该疾病的临床管理中的一种未满足的需求。成像技术目前是此类监控的黄金标准。但是，关于所需的成像类型和频率。成像很昂贵，耗时，检测疾病变化缓慢并引起人们对重复辐射暴露和成本的担忧，并不总是被保险所承保的。标准中使用了成像的互补方法，例如循环肿瘤细胞和生物标志物护理（SOC），尽管他们的应用仍然有限。一个简单，成本效益的血液测试，用于测量水平疾病侵略性的驱动力的生物标志物应为实时提供新颖的解决方案监测治疗反应并减少对MBC人群中成像的依赖。 PI已确定 88KDA糖蛋白GP88（progranulin）阐明了其生物活性作为自分泌生长和生存因素。 GP88从癌细胞中分泌，可在乳腺癌较高水平的生物液中测量与健康个体相比，患者。基于这些特征，创新的诊断测试（酶免疫测定 - EIA）在循环中测量GP88。我们的SBIR第1阶段回顾性研究证明了通过EIA测试测量的血清GP88水平与客观之间的统计关联疾病的度量，即101名MBC患者中的1.1。我们确定血清GP88水平为56ng/ml 是一个分层，在该分层以下患者的总生存率提高，而GP88> 56 ng/ml的患者结果很差。我们表明，血清GP88水平在统计学上与对治疗的反应相关与SOC生物标志物CA15-3不同，疾病的进展仅与仅与疾病。基于这些承诺数据，我们提出了SBIR第2阶段的前瞻性纵向研究每月测量血清GP88水平，在两个临床部位注册120名MBC患者的15个月期间每3个月进行一次成像。目的是验证第1阶段的发现并建立在监测MBC患者疾病进展/反应中的GP88测试作为辅助成像和帮助此类患者的临床管理。具体来说，我们将（1）验证该血清GP88 水平与成像结果定义的疾病反应/进展相关；（2）检查成功的高（> 56ng/ml）和低（<56ng/ml）GP88血液水平在未来的反应/进展和时间上成像结果所定义的进展；（3）验证一致的低（<56ng/ml）GP88的患者与始终高（> 56ng/ml）GP88血液的患者相比，血液水平的生存率提高了水平。该阶段2的结果将是建立临床数据以支持GP88 EIA的商业化作为MBC患者临床管理不可或缺的一部分，将有助于改善MBC患者的护理以降低的成本。