Immune and Inflammatory Biomarkers in Radiotherapy-Induced Skin Toxicities

放射治疗引起的皮肤毒性中的免疫和炎症生物标志物

• 批准号: 8895684
• 负责人: Jennifer J Hu
• 金额: $ 7.68万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8895684
• 关键词: Adjuvant Radiotherapy; Adverse effects; Adverse reactions; African American; Age; American; Anti-Inflammatory Agents; Biological Assay; Biological Markers; Body mass index; Breast; Breast Cancer Patient; C-reactive protein; Cancer Etiology; Cessation of life; Clinical; Clinical Data; Data; Development; Diagnostic; Diagnostic Neoplasm Staging; Dose; Ensure; Environment; Epidemiologist; Epidemiology; Ethnic Origin; Ethnic group; Fibrosis; Funding; Future; Goals; Hispanics; Immune; Immune response; Immunosuppressive Agents; Immunotherapy; Individual; Inflammation; Inflammatory; Inflammatory Response; Knowledge; Laboratories; Late Effects; Learning; Malignant Neoplasms; Medial; Medical; Minority; Modeling; Molecular; Molecular Genetics; Normal tissue morphology; Not Hispanic or Latino; Obesity; Outcome; Outcomes Research; Patients; Plasma; Population; Positioning Attribute; Postoperative Period; Predictive Value; Quality of life; Race; Radiation Tolerance; Radiation therapy; Reaction; Recurrence; Research; Research Project Grants; Resources; Sampling; Second Primary Cancers; Skin; Smoking Status; Target Populations; Testing; Toxic effect; Transforming Growth Factor beta; Tumor stage; Underrepresented Minority; Validation; Variant; Woman; Work; anticancer research; base; cancer diagnosis; cancer health disparity; cost effective; cytokine; design; experience; health disparity; high risk; improved; inhibitor/antagonist; innovation; innovative technologies; malignant breast neoplasm; mortality; patient population; personalized intervention; personalized medicine; personalized therapeutic; precision medicine; prevent; public health relevance; racial and ethnic; racial/ethnic difference; response; tool; treatment response

 DESCRIPTION (provided by applicant): Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Postoperative adjuvant radiotherapy (RT) significantly reduces local-regional recurrence and breast cancer death. However, some patients experience moist desquamation as early adverse skin reactions (EASRs) and fibrosis as late effect. Underserved minorities are less likely than Whites to receive the recommended adjuvant RT and if treated, have a higher risk for developing RT-related EASRs and worse clinical outcomes. Therefore, to achieve our long-term goals in improving quality of life and reducing breast cancer mortality, the primary objective of the proposed research is to develop and validate two immune and inflammatory biomarkers in predicting RT-induced EASRs and quality of life. We will test the overall working hypothesis that worse clinical outcomes, such as RT-induced EASRs, late effects, and recurrence occur more frequently in women with: (i) modulated immune response and (ii) stimulated inflammation and hyper-radio-sensitivity. We will test a new paradigm that combined immune and inflammatory responses contribute to individual variations in radio-sensitivity that may predict RT-induced adverse reactions and clinical outcomes. Investigating this new paradigm will develop powerful tools in identifying high-risk populations and targets for personalized intervention and therapeutic strategies, such as immunotherapies and anti-inflammatory agents. Capitalizing on existing plasma samples and extensive clinical data from 1,200 breast cancer patients (400 black or African Americans, 400 Hispanic Whites, and 400 non-Hispanic Whites), this extremely cost-effective proposed research will be the first and the largest tri-racial/ethnic study evaluating th association between RT- induced EASRs and: (i) a pleiotropic immunosuppressive cytokine, transforming growth factor-beta (TGF-ß), (ii) an inflammatory biomarker, C-reactive protein (CRP), and (iii) the combined effects of TGF-ß and CRP after adjustment for potential confounders or effect modifiers, such as age, race/ethnicity, body mass index, tumor stage, smoking status, other medical conditions, RT dose, and breast volume. Capitalizing on the existing samples and clinical data from a large breast cancer patient population, promising pilot data, strong institutional support, and established laboratory assays, we are in an exceptional position to carry out the proposed research. Overall Impact: Using a hypothesis-driven strategy to rationally design the proposed research, the anticipated outcome will significantly impact the desperately needed innovative biomarker development and validation for basic, preventative, diagnostic, translational, epidemiological, health disparities, and clinical cancer research. As we learn more about underlined molecular mechanisms of RT-induced EASRs and clinical outcomes, the knowledge gained will significantly impact precision medicine and ensure that every breast cancer patient gets the most optimal treatment(s) with maximal efficacy and minimal side effects, particularly in underserved minorities with worse treatment response, side effects, and survival.

 描述（由适用提供）：乳腺癌是美国女性最常见的癌症，是癌症死亡的第二大原因。后辅助放疗（RT）显着降低了局部区域复发和乳腺癌死亡。但是，一些患者随着早期不良皮肤反应（EASRS）和纤维化的潮湿而潮湿的脱水效果。服务不足的少数民族比白人接受建议的可调节RT的可能性要小，并且如果接受治疗，患有RT相关的EASR和较差的临床结果的风险更高。因此，为了实现我们在改善生活质量和降低乳腺癌死亡率的长期目标，拟议研究的主要目标是开发和验证两种免疫和炎症生物标志物，以预测RT诱导的EASR和生活质量。我们将测试临床较差的总体工作假设。在患有：（i）调节免疫响应和（ii）刺激的注射和超哈迪奥敏感性的女性中，诸如RT诱导的EASR，晚期效应和复发等结果更频繁。我们将测试一种新的范式，将免疫力和炎症反应组合起来有助于无线敏感性的个体变化，这可能预测了RT诱导的不良反应和临床结果。调查这一新范式将开发出强大的工具，以确定个性化干预和治疗策略的高风险人群和目标，例如免疫疗法和抗炎药。利用来自1,200名乳腺癌患者（400名黑人或非裔美国人，400名西班牙裔白人和400个非西班牙裔白人）的现有血浆样品和大量临床数据，这项极具成本效益的研究将是第一和最大的三 - 种族/种族研究，评估RT诱导的EASR和ISPERINGE cYRESU的cyiotrs cyiotrs cyiotr cyiotr cyiotr cyiotr cyiotr cyiotr cyiotr cyiotr cyiotr，I） transforming growth factor-beta (TGF-ß), (ii) an inflammatory biomarker, C-reactive protein (CRP), and (iii) the combined effects of TGF-ß and CRP after adjustment for potential confounders or effect modifiers, such as age, race/ethnicity, body mass index, tumor stage, smoking status, other medical conditions, RT dose, and breast volume.利用来自大型乳腺癌患者人群的现有样品和临床数据，有希望的试点数据，强大的机构支持以及已建立的实验室测定，我们处于非凡的位置，可以进行拟议的研究。总体影响：使用假设驱动的策略合理地设计拟议的研究，预期的结果将显着影响迫切需要创新的生物标志物发展和对基本，预防，诊断，转化，流行病学，健康差异和临床癌症研究的验证。像我们 了解有关RT诱导的EASR和临床结果的下划线分子机制的更多信息，获得的知识将显着影响精度医学，并确保每个乳腺癌患者获得最佳的最佳治疗（S），具有最大的有效性和最小的副作用，尤其是在缺乏较低的少数群体中，较差的治疗疗法，副作用，副作用和生存。