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.

我们研究计划的总体目标是了解三阴性的分子异质性 乳腺癌（TNBC），识别和验证具有预后和预测作用的生物标志物， 最终根据每位患者的肿瘤生物学特性优化治疗方案。朝这个方向 最后，我们最近收到了资金来进行一项由研究者发起的前瞻性临床试验，题为 三阴性乳腺癌微小残留病 (AIM-TNBC) 的辅助强化治疗 评估术后残留病灶的 TNBC 患者强化辅助全身治疗 新辅助全身治疗。在 Natera, Inc. 的行业支持下，我们将使用个性化流通 肿瘤 DNA (ctDNA) 分析可识别具有微小残留病的患者，然后对这些患者进行随机分组 高危患者接受标准护理与强化辅助治疗。我们本次 KIPM 的具体目标 COBRE 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（ncRNA）作为最小的额外生物标志物 在我们的前瞻性 AIM-TNBC 试验中定义高风险 MRD 特征的残留疾病，以及 (2) 了解分子生物标志物信息如何影响 TNBC 患者的认知 个体复发风险和接受辅助治疗的意愿。这项工作最终将得到改善 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 的使命是一致的：提供精确的 医学的特点是它考虑了疾病分子组成的个体差异，旨在 根据每位患者独特的生物学特征制定治疗方案。