Detection of MRD in TNBC Through Multi-Platform Molecular Biomarker Analysis

通过多平台分子生物标志物分析检测 TNBC 中的 MRD

• 批准号: 10580880
• 负责人: Steven Allan Soper
• 金额: $ 12.16万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-18 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10580880
• 关键词: Adjuvant; Adjuvant Therapy; Biological Markers; Biology; Breast Cancer Patient; Centers of Research Excellence; Clinical Trials; DNA analysis; Detection; Disease; Funding; Goals; Heterogeneity; Individual; Industry; Institutes; Kansas; Mission; Molecular; Neoadjuvant Therapy; Neoplasm Circulating Cells; Patients; Perception; Plasma; Randomized; Research; Research Personnel; Residual Neoplasm; Residual Tumors; Systemic Therapy; Tumor Biology; Untranslated RNA; Work; base; extracellular vesicles; high risk; improved; individual variation; individualized medicine; molecular marker; precision medicine; prognostic; programs; prospective; relapse risk; risk stratification; standard of care; treatment optimization; triple-negative invasive breast carcinoma; tumor DNA; willingness

The overarching goal of our research program is to understand the molecular heterogeneity of triple-negative breast cancer (TNBC), to identify and validate biomarkers that are both prognostic and predictive, and ultimately to optimize treatment for each patient based on the biology of her/his tumor. Towards this end, we have recently received funding to conduct a prospective investigator-initiated clinical trial entitled Adjuvant Intensification for Minimal Residual Disease in Triple-Negative Breast Cancer (AIM-TNBC) that is evaluating intensification of adjuvant systemic therapy in TNBC patients with residual disease after neoadjuvant systemic therapy. With industry support from Natera, Inc., we will use personalized circulating tumor DNA (ctDNA) analysis to identify patients with minimal residual disease and then randomize these high-risk patients to standard-of-care versus intensified adjuvant therapy. Our specific aims for this KIPM COBRE application are (1) to evaluate circulating tumor cells (CTCs) and non-coding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EVs) as additional biomarkers of minimal residual disease to define a high-risk MRD signature in our prospective AIM-TNBC trial and (2) to understand how molecular biomarker information influences TNBC patients’ perception of individual relapse risk and willingness to accept adjuvant therapy. This work will ultimately improve our ability to risk-stratify TNBC patients and identify those who are likely to benefit from intensification of adjuvant systemic therapy. This goal is aligned with the KIPM COBRE’s mission of providing precision medicine in that it considers individual variability in the molecular composition of one’s disease and aims to tailor treatment towards each patient’s unique biology.

我们研究项目的首要目标是了解三阴性的分子异质性