Micro-Organospheres Drug Screen to Lead Care (MODEL): a Precision Oncology Platform to Guide Breast Cancer Therapy

微有机球药物筛选引导护理 (MODEL)：指导乳腺癌治疗的精准肿瘤学平台

• 批准号: 10836600
• 负责人: Daniel Delubac
• 金额: $ 99.85万
• 依托单位: XILIS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-09 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10836600
• 关键词: Address; Adoption; Automation; Biological Assay; Biology; Biopsy; Breast Cancer Detection; Breast Cancer Patient; Breast Cancer therapy; Cancer Diagnostics; Cancer Patient; Caring; Cells; Clinic; Clinical; Clinical Data; Clinical Laboratory Improvement Amendments; Clinical Protocols; Clinical Research; Complex; Development; Devices; Drug Screening; ERBB2 gene; Emulsions; Face; Fine needle aspiration biopsy; Funding; Future; Gel; Generations; Genomics; Goals; Institutional Review Boards; Lead; Malignant Neoplasms; Medicine; Methods; Microfluidics; Minority; Modeling; Needle biopsy procedure; Neoadjuvant Therapy; Oncologist; Oncology; Organoids; Outcome; Patients; Performance; Pharmaceutical Preparations; Phase; Predisposition; Process; Refractory; Regimen; Risk; Robotics; Running; Sample Size; Sampling; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Validation; Work; arm; cancer therapy; cancer type; clinical diagnostics; clinical predictors; commercialization; cost; data integration; data integrity; design; diagnostic assay; drug testing; experience; feasibility testing; flexibility; improved; individual patient; malignant breast neoplasm; microfluidic technology; miniaturize; neoplastic cell; novel; novel strategies; participant enrollment; patient response; patient screening; precision oncology; predicting response; predictive modeling; prototype; research clinical testing; response; scale up; screening; standard of care; success; technology platform; treatment response; tumor; validation studies

PROJECT SUMMARY/ABSTRACT The goal of precision oncology is to match cancer patients with medicines based on the specific biology of their tumor. Crucially, the current precision oncology paradigm – which is largely based on tumor genomic profiling – doesn’t work for the majority of patients. Since every patient’s tumor is uniquely complex, a potential solution to this “precision” problem involves creating a viable functional model of a patient’s individual tumor in order to directly test its susceptibility to different drugs. The broad adoption of such patient-derived functional models into the clinic thus far has been hindered by several limitations centered on scalability, time, and success rate. Specifically, any assay for guiding therapy must be: i) amenable to the amount of material derived from needle biopsies, ii) established with a high success rate, and iii) completed within 10-14 days to minimize unacceptable treatment delays. To address these clinical limitations, we have developed the novel Micro-Organosphere Drug Screen to Lead Care (MODEL) platform. MODEL is based on novel microfluidics technology that generates Patient-Derived Micro-Organospheres (PDMO) from clinical samples (e.g., biopsies) and performs drug screening within 10 days to guide therapy. The objective of our proposal is to further develop and validate our MODEL technology in breast cancer, with a view to advancing it further towards becoming a standard of care diagnostic assay. Phase I of our proposal will focus on preparing our MODEL device for rigorous clinical evaluation. In Aim 1 we will make key upgrades to our device prototype to improve sample efficiency, device performance, and operability. Specifically, the goal of these improvements will be to reduce sample size requirements (extending our capabilities down to fine-needle aspirates), enhance device performance, reinforce consistency of key parameters during and between runs, and increase process automation. In Aim 2, we will rigorously test the ability of our second-generation device to i) successfully generate PDMO from breast cancer biopsies and ii) perform drug screens in less than 10 days total. In Phase II, we will make key device upgrades to prepare the MODEL platform for commercialization, focusing on improving features related to data integrity and ease-of-use (Aim 1). In Aim 2 we will perform the first validation of our MODEL platform in a HER2+ breast cancer clinical protocol consisting of 50 patients, with the goal of testing MODEL’s ability to predict response to standard of care neoadjuvant therapy. If successful, the development of our platform will revolutionize precision oncology by arming oncologists with the information needed to optimally match cancer patients with medicines.

项目摘要/摘要 精确肿瘤学的目标是根据癌症患者的特定生物学特征将他们与药物相匹配。 肿瘤。至关重要的是，目前的精确肿瘤学范式--主要基于肿瘤基因组图谱-- 对大多数病人都不起作用。由于每个患者的肿瘤都是独一无二的复杂，一个潜在的解决方案 这一“精确度”问题涉及到创建患者个体肿瘤的可行功能模型，以便 直接检测其对不同药物的敏感性。这种患者派生的功能模型在 到目前为止，临床一直受到以可伸缩性、时间和成功率为中心的几个限制。 具体地说，任何用于指导治疗的化验必须：i)服从从针头中提取的材料的量 活检，ii)建立高成功率，以及iii)在10-14天内完成，以最大限度地减少不可接受 治疗延误。为了解决这些临床局限性，我们开发了新型微有机微球药物 引导关怀(模型)平台的屏幕。该模型基于新的微流体技术，可以产生 从临床样本(例如，活组织检查)中提取患者衍生的微有机微球(PDMO)并执行药物 在10天内进行筛查以指导治疗。我们建议的目标是进一步开发和验证我们的 乳腺癌的模型技术，以期进一步推动其成为护理的标准 诊断化验。我们计划的第一阶段将专注于为严格的临床准备我们的模型设备 评估。在目标1中，我们将对我们的设备原型进行关键升级，以提高样本效率 性能和可操作性。具体地说，这些改进的目标将是减少样本量 要求(将我们的能力向下扩展到细针抽吸物)，提高设备性能，加强 在运行期间和运行之间保持关键参数的一致性，并提高过程自动化。在目标2中，我们将 严格测试我们的第二代设备的能力，以i)成功地从乳腺癌产生PDMO 活检和ii)在总共不到10天的时间内进行药物筛选。在第二阶段，我们将进行关键设备升级 为商业化准备模型平台，重点改进与数据完整性相关的功能 和易用性(目标1)。在目标2中，我们将在HER2+乳房中执行我们的模型平台的第一次验证 由50名患者组成的癌症临床方案，目标是测试模型预测对 新辅助治疗的标准护理。如果成功，我们平台的开发将带来革命性的变化 精确肿瘤学通过向肿瘤学家提供所需的信息，使癌症患者与 药物。