Developing targeted therapy with prostate cancer specific nanomedicine

开发前列腺癌特异性纳米药物的靶向治疗

基本信息

批准号：
8615933
负责人：
Jer-Tsong Hsieh
金额：
$ 32.79万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8615933
关键词：
Ablation Address Adverse effects Affinity Age Aging American Androgens Animal Model Antineoplastic Agents Area Biocompatible Biocompatible Materials Cancer Patient Castration Cell Death Cell model Cells Clinical DNA Damage Detection Development Disease Drug Delivery Systems Drug resistance Engineering FDA approved Goals Heterogeneity Image Investigational Therapies Kidney Knowledge Left Legal patent Liver Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of prostate Medicine Metastatic Lesion Metastatic Prostate Cancer Modeling Monitor Mus Mutagens Nanotechnology Neoplasm Metastasis Outcome Outcome Study Patients Peptides Phenotype Polymers Prevention Property Prostatic Neoplasms Quality of life R peptide Radiation Recurrence Regimen Reporting Research Resistance Solid Neoplasm Specificity Spleen Structure of base of prostate System Technology Therapeutic Therapeutic Agents Time Treatment Efficacy base biodegradable polymer cancer cell cancer initiation cancer recurrence cancer stem cell cancer therapy castration resistant prostate cancer cell type chemotherapeutic agent chemotherapy combat cytolethal distending toxin deprivation design early onset effective therapy fluorescence imaging improved in vivo innovation intravenous injection killings men molecular imaging mortality nanomedicine nanoparticle neoplastic cell novel therapeutics physical conditioning poly(lactide)pre-clinical prevent prostate cancer cell public health relevance response self-renewal stem cell population stem cells theories therapy development tumor tumor progression uptake

项目摘要

Project Summary Prostate cancer (PCa) has surpassed lung cancer as the leading cancer among American men. The majority of patients have already developed metastatic lesions at initial clinical presentation and androgen ablation has become a standard therapy because PCa is an androgen-dependent (AD) disease. Inevitably, the recurrence of castration resistant PCa (CRPC) will result in mortality of patients since CRPC cells are resistant to conventional chemotherapy. Moreover, because of high age, PCa patients often do not have favorable physical conditions to tolerate undesirable side effects of chemotherapy. Thus, developing a new, safe and effective therapy becomes a high priority. Although PCa patient survival with newly developed therapeutic regimens has been significantly improved, PCa remains incurable. One of the possible theories to explain the recurrence and ineffectiveness of cancer treatment is the cancer stem cell (CSC) model in which a subset of tumor cells is responsible for cancer initiation and progression as well as cancer recurrence. These CSCs share with normal stem cells the properties of self-renewal, immortal and differentiation into a variety of cell types including heterogeneous lineages of cancer cells. Also, CSC can re-grow from a few cells left behind after therapy, it will be important to develop therapies that are more specifically directed against CSCs. Thus, targeting cancer stem cell is now becomes an active research area of cancer therapy to achieve the ultimate cure. In order to target PCa specifically, we are developing a new biodegradable and biocompatible nanoparticle that can target PCa specifically with imaging capabilities. Using this unique delivery system, we propose to engineer a unique genotoxin that can preferentially kill PCa cells expressing stem cell properties then evaluate the therapeutic efficacy of PCa monitored by molecular imaging in pre-clinical animal models. We expect be able to monitor the drug delivery and/or response of cancer cells in a real-time manner. This experimental therapy could become a better regimen for treating CRPC because this agent has a PCa specificity, which is expected to be less toxic than chemotherapeutic agents. Most importantly, this proposal is to explore a new avenue of tailored therapy in contrast to conventional therapeutic strategy; we expect that the outcome of this study should have an immediate clinical impact on CRPC therapy.

项目摘要前列腺癌（PCA）已超过肺癌，成为美国男性的主要癌症。大多数患者在最初的临床表现和雄激素消融已成为一种标准疗法，因为PCA是雄激素依赖性的（AD）疾病。不可避免的是，耐can抑制PCA（CRPC）的复发将导致患者死亡由于CRPC细胞对常规化疗具有抗性。而且，由于年龄较高，PCA 患者通常没有有利的身体状况来耐受的副作用化学疗法。因此，开发一种新的，安全有效的疗法成为高度重视。尽管新开发的治疗方案的PCA患者生存率已显着改进的PCA仍然无法治愈。解释复发的可能理论之一和癌症治疗的无效性是癌症干细胞（CSC）模型，其中一部分肿瘤细胞负责癌症的启动和进展以及癌症复发。这些CSC 与正常干细胞共享自我更新，不朽和分化的特性细胞类型，包括癌细胞异质谱系。另外，CSC可以从几个单元格中重新生长治疗后留在后面，开发更明确指导的疗法将很重要反对CSC。因此，靶向癌症干细胞现在成为癌症的活跃研究领域治疗以实现最终治疗。为了特别针对PCA，我们正在开发一个新的可生物降解且可生物相容性的纳米颗粒，可以专门针对PCA成像功能。使用这种独特的输送系统，我们建议设计一种独特的基因毒素，可以优先杀死表达干细胞特性的PCA细胞，然后评估监测的PCA的治疗功效通过临床前动物模型中的分子成像。我们希望能够监控药物输送和/或癌细胞以实时方式的反应。这种实验疗法可能成为更好地治疗CRPC的更好的方案，因为该试剂具有PCA特异性，预计将是比化学治疗剂毒性较小。最重要的是，该提议是探索新的途径与常规治疗策略相比，量身定制的疗法；我们期望这一结果研究应立即对CRPC治疗产生临床影响。