Development of a novel personalized medicine platform using apheretically isolated circulating tumor cells to assess drug responsiveness in prostate cancer

开发一种新型个性化医疗平台，使用非血浆分离的循环肿瘤细胞来评估前列腺癌的药物反应

• 批准号: 10384366
• 负责人: Justin Michael Drake
• 金额: $ 39.97万
• 依托单位: ASTRIN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384366
• 关键词: American; BRAF gene; Biological Assay; Biological Markers; Biological Sciences; Biopsy; Blood; Blood Circulation; Blood Component Removal; Blood Volume; Cancer Etiology; Cancer Patient; Cardiovascular system; Cell Count; Cell Separation; Cell Survival; Cells; Cessation of life; Clinical; Computer software; Custom; Data; Detection; Development; Devices; Diagnosis; Disease; Disseminated Malignant Neoplasm; Distant; Drug Targeting; Epidermal Growth Factor Receptor; Erlotinib; Erythrocytes; Excision; Gene Expression; Gene Proteins; Gene set enrichment analysis; Genes; Genome; Genomics; Goals; Heterogeneity; Hour; Image; Immune Targeting; Individual; Intelligence; Intervention; Knowledge; Laboratories; Leukapheresis; Lymphatic System; Machine Learning; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Maps; Metastatic Prostate Cancer; Methods; Microfluidics; Mononuclear; Mutation; Neoplasm Circulating Cells; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phase; Phenotype; Plasma; Population; Precision therapeutics; Preparation; Primary Neoplasm; Prior Therapy; Procedures; Process; Progression-Free Survivals; Prostate Cancer therapy; Proteomics; Reporting; Resistance; Safety; Sample Size; Sampling; Signal Pathway; Signal Transduction; Site; Small Business Technology Transfer Research; Specimen; Stream; Survival Rate; System; Techniques; Technology; Testing; Therapeutic; United States; base; cancer cell; cancer therapy; castration resistant prostate cancer; clinical implementation; comparative; comparative efficacy; cost; density; driver mutation; drug candidate; drug testing; enzalutamide; genetic signature; hologram; improved; individualized medicine; machine learning classifier; melanoma; neutrophil; novel; novel strategies; personalized medicine; precision drugs; precision medicine; single-cell RNA sequencing; standard of care; stem cells; success; targeted agent; targeted treatment; therapeutic target; transcriptomics; treatment response; tumor

Project Summary Metastatic prostate cancer is a notoriously heterogeneous disease that is difficult to treat. The five-year survival rate has not improved over the past twenty-five years and the median survival rate for those diagnosed with metastatic castration resistant prostate cancer (mCRPC) is only 15-36 months. Precision medicine has the potential to improve mCRPC outcomes. Transciptomic sequencing of circulating tumor cells (CTCs) can provide important information regarding metastatic disease and is an attractive alternative to serial biopsies of metastatic lesions as biopsies are difficult for sick patients to endure and they do not always yield a viable tumor specimen for analysis. Metastatic lesions are often established from CTC progenitors seeding a distant site through the bloodstream or lymphatic system. Current methods for extracting and analyzing CTCs from the bloodstream are clinically limited as they are expensive, inefficient, and do not yield enough CTCs to capture actionable biomarkers, often only obtaining 10 CTCs per procedure. Thus, there remains a major unmet need to improve the technologies that can identify and isolate CTCs from the bloodstream of patients with metastatic disease. Astrin Biosciences will improve upon current CTC technologies by developing a novel individualized medicine platform that uses apheresis to isolate CTCs. A Machine Learning classifier built upon quantitative holograms intelligently identifies and filters large numbers of CTCs that are viable for ex vivo drug testing. The Astrin Biosciences platform can capture and analyze 10,000 CTCs with a single procedure, providing an opportunity for comprehensive representation of the heterogeneity of mCRPC. This process allows for improved determination of activated pathways that will help infer precision drug targets that can be tested on the patient’s own cancer cells. Knowledge of the optimal course of therapy prior to systemic drug administration will improve response to therapy at a lower cost to the system. This proposal thus aims to do the following: 1) assess feasibility for aphaeretic extraction of large numbers of CTCs from patients with mCRPC and 2) complete comparative profiling and ex vivo viability testing of cultured CTCs. This platform could shift the current paradigm of metastatic prostate cancer treatment and offer a novel approach to improve the poor 5-year survival rate of mCRPC.

项目总结