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 乳腺癌（TNBC），以确定和验证生物标志物，既预后和预测， 并最终基于她/他的肿瘤的生物学来优化每个患者的治疗。为实现这一 最后，我们最近收到了一笔资金，用于进行一项前瞻性的、由制药商发起的临床试验， 三阴性乳腺癌微小残留病的辅助强化治疗（AIM-TNBC）， 评估TNBC患者术后残留疾病的强化辅助全身治疗 新辅助全身治疗。在Natera，Inc.的行业支持下，我们将使用个性化的循环 肿瘤DNA（ctDNA）分析，以确定有微小残留病变的患者，然后将这些患者随机分组， 高危患者接受标准治疗与强化辅助治疗。我们对KIPM的具体目标 COBRE的应用是（1）评估循环肿瘤细胞（CTC）和非编码RNA 血浆来源的细胞外囊泡（EV）中的非编码RNA（ncRNA）作为最小细胞内毒素的额外生物标志物。 在我们的前瞻性AIM-TNBC试验中，残留疾病定义高风险MRD特征，以及（2） 了解分子生物标志物信息如何影响TNBC患者对 个体复发风险和接受辅助治疗的意愿。这项工作最终将改善 我们有能力对TNBC患者进行风险分层，并确定那些可能从强化治疗中受益的患者。 辅助全身治疗。这一目标与KIPM COBRE的使命一致， 医学，因为它考虑了一个人的疾病的分子组成的个体差异，并旨在 针对每个病人的独特生物学特性进行量身定制的治疗。