Functional Significance of CD133 in Pancreatic Cancer

CD133 在胰腺癌中的功能意义

• 批准号: 9304048
• 负责人: Sulagna Banerjee
• 金额: $ 31.85万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9304048
• 关键词: Affect; Aftercare; Animal Model; Animals; Applications Grants; Biological; Biological Assay; Biological Process; CXCR4 gene; Cancer Etiology; Cell Line; Cell physiology; Cell surface; Cells; Cessation of life; Characteristics; Data; Development; Disease; Down-Regulation; Evaluation; Event; Grant; In Vitro; Invaded; Laboratories; Lead; Malignant neoplasm of pancreas; Membrane Proteins; Molecular; Neoplasm Metastasis; Organ; Pancreatic Ductal Adenocarcinoma; Pathway interactions; Patients; Phase I Clinical Trials; Phenotype; Play; Population; Prevention; Prodrugs; Property; Proteins; Recurrence; Regimen; Regulation; Relapse; Reporting; Resistance; Role; Surface; Survival Rate; Therapeutic; Time; Tumor Cell Invasion; Tumor Initiators; Tumor Markers; Tumorigenicity; United States; Up-Regulation; Variant; Water; analog; base; cancer cell; cancer stem cell; chemotherapeutic agent; chemotherapy; improved; in vivo; ineffective therapies; migration; mouse model; novel therapeutics; outcome forecast; overexpression; pancreatic cancer cells; pancreatic neoplasm; preclinical study; prevent; public health relevance; stem; targeted agent; translational study; treatment strategy; triptolide; tumor; tumor initiation; tumorigenic

DESCRIPTION (provided by applicant): Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth most frequent cause of cancer related deaths in United States due to propensity to metastasis, invasion and resistance to chemotherapy. All stage 5-year survival rate is <5% with over 95% of the patients having recurrence of the tumor either locally or in the form of metastasis to other organs. Tumor relapse has been largely attributed to the presence of tumor initiating cells (TIC) or cancer stem cells (CSC). CSCs or TICs are quiescent cells within a tumor that are resistant to chemotherapy and are responsible for tumor recurrence. Thus therapies directed against TICs should lead to decreased tumor recurrence and metastases. Unfortunately, currently no chemotherapeutic agents are known to target TICs. CD133 is one of the surface markers that have been used in isolation and characterization of pancreatic tumor initiating cells. However, the biological role of CD133 is not known. Our group has recently evaluated Minnelide, a water soluble pro-drug of triptolide in pre-clinical studies on multiple animal models of pancreatic cancer with very promising results. However, the effect of Minnelide on prevention of tumor recurrence has not been studied in great detail. The current proposal is focused on elucidating the downstream events that are triggered by CD133 expression on a tumor initiating cell resulting in tumor recurrence and invasion leading to metastasis in this disease and evaluating the effect of Minnelide on this cell population.

描述（由申请方提供）：胰腺导管腺癌（PDAC）目前是美国癌症相关死亡的第四大最常见原因，原因是转移倾向、侵袭和化疗耐药性。所有阶段的5年生存率<5%，超过95%的患者局部复发或以转移到其他器官的形式复发。肿瘤复发主要归因于肿瘤起始细胞（TIC）或癌症干细胞（CSC）的存在。CSC或TIC是肿瘤内的静止细胞，其对化疗具有抗性并且是肿瘤复发的原因。因此，针对TIC的治疗应导致减少肿瘤复发和转移。不幸的是，目前已知没有靶向TIC的化疗剂。CD133是胰腺肿瘤起始细胞分离和鉴定的表面标志物之一。然而，CD133的生物学作用尚不清楚。我们的小组最近评估了Minnelide，雷公藤内酯醇的水溶性前药在胰腺癌的多个动物模型的临床前研究中具有非常有希望的结果。然而，Minnelide对预防肿瘤复发的作用尚未进行详细研究。目前的建议集中在阐明由肿瘤起始细胞上的CD133表达触发的下游事件，导致肿瘤复发和侵袭，导致该疾病的转移，并评估Minnelide对该细胞群体的影响。