A microfluidic cell culture platform for personalizing pancreatic cancer therapies

用于个性化胰腺癌治疗的微流控细胞培养平台

• 批准号: 10155447
• 负责人: Alexander Revzin
• 金额: $ 29.1万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10155447
• 关键词: 3-Dimensional; Address; Automation; Biosensing Techniques; Biosensor; CA-19-9 Antigen; Cancer Biology; Cancer Etiology; Cell Culture Techniques; Cells; Cessation of life; Characteristics; Chemoresistance; Chemotherapy-Oncologic Procedure; Clinic; Clinical; Collagen; Consensus; Detection; Development; Devices; Diagnosis; Diagnostic radiologic examination; Digestion; Dimensions; Disease; Drug resistance; E-Cadherin; Enrollment; Epithelial; Extracellular Matrix; Fibroblasts; Future; Gel; Generations; Goals; Guidelines; Heterogeneity; Image; Immunoassay; Incidence; Life Expectancy; Maintenance; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Microfluidic Microchips; Microfluidics; Mutation; Newly Diagnosed; Oncology; Paclitaxel; Patients; Pharmaceutical Preparations; Phenotype; Process; Reagent; Regimen; Resistance; Retrieval; Selection for Treatments; Sonal; Survival Rate; System; TNF gene; Testing; Time; TimeLine; Treatment Protocols; United States; Work; cancer cell; cancer therapy; cellular engineering; chemotherapy; cytotoxicity; design; efficacious treatment; experience; experimental study; gemcitabine; improved; individual patient; matrigel; mouse model; novel; pancreatic cancer cells; patient derived xenograft model; patient response; personalized chemotherapy; personalized medicine; response; tool; treatment response; tumor; validation studies

Pancreatic cancer is expected to become the second leading cause of cancer death in the United States by 2030. Because this cancer is asymptomatic at the early stage, patients are diagnosed at the advanced stage and have a 5 year survival rate of less than 5%. The benefit from `one-size-fits-all' approach to treating pan- creatic cancer has reached a plateau, partly due to high incidence of chemotherapy resistance and heterogeneity associated with this disease. Novel tools are needed to address these problems and to improve the survival of patients afflicted by this deadly cancer. About 40% of newly diagnosed patients have a metastatic form of pancreatic cancer. Typical survival time for such patients is between 8 and 10 months; therefore, it is extremely important to initiate the most efficacious therapy as soon as possible. All patients with metastatic pancreatic cancer receive a chemotherapy regimen. A patient is enrolled into either a FOLFIRINOX or gemcitabine/nab-paclitaxel regimen. At the present time, the decision of which chemotherapy regimen to use is driven by general consensus guidelines and not by the tu- mor characteristics of an individual patient. Treatment response is typically evaluated by radiographical imaging performed every two months, and only 30% of patients respond to the chosen chemotherapy regimen. Precious time is lost as a result. Such trial-and-error approach to therapy selection for treating an aggressive cancer is simply unacceptable. Our team proposes to accelerate and personalize therapy selection process by developing a microfluidic platform for cultivating cancer cells and evaluating drug responsiveness for patients with metastatic pancreatic cancer. Our long term goal is to establish clinical utility of microfluidic cancer cul- tures for personalizing chemotherapy. Upon successful completion of the current project, the microfluidic culture platform will be incorporated into future clinical validation studies.

胰腺癌预计将成为美国癌症死亡的第二大原因， 2030.因为这种癌症在早期是无症状的，病人在晚期才被诊断出来 5年存活率不到5%“一刀切”处理泛非问题的办法的好处 Creatic癌症已经达到了一个平台，部分原因是化疗耐药性的高发病率， 与这种疾病相关的异质性。需要新的工具来解决这些问题， 这种致命癌症患者的生存。 大约40%的新诊断患者患有转移性胰腺癌。典型生存时间 这类患者的年龄在8至10个月之间;因此，启动最有效的 尽快治疗。所有转移性胰腺癌患者均接受化疗方案。 将患者招募到FOLFIRINOX或吉西他滨/nab-紫杉醇方案中。目前的 使用哪种化疗方案的决定是由普遍共识指南而不是由实际情况决定的。 莫尔的是个体患者的特征。治疗反应通常通过放射学检查评估 每两个月进行一次成像，只有30%的患者对所选择的化疗方案有反应。 宝贵的时间因此而丧失。这种用于治疗侵袭性肿瘤的治疗选择的试错法是不可行的。 癌症是不可接受的。我们的团队建议通过以下方式加速和个性化治疗选择过程： 开发用于培养癌细胞和评估患者药物反应性的微流体平台 转移性胰腺癌我们的长期目标是建立微流控癌症细胞的临床实用性， 个性化化疗的方法在成功完成当前项目后， 培养平台将纳入未来的临床验证研究。

项目成果

Patient-Specific Microfluidic Cancer Spheroid Cultures for Testing Cancer Therapies.

用于测试癌症治疗的患者特异性微流体癌症球体培养物。

• DOI: 10.1007/978-1-0716-3271-0_15
• 发表时间: 2023
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Choi,Daheui;Gonzalez-Suarez,AlanM;Billadeau,DanielD;Ma,WenWee;Stybayeva,Gulnaz;Revzin,Alexander
• 通讯作者: Revzin,Alexander