Ultrasound enhanced penetration for treatment of pancreatic cancer

超声增强穿透治疗胰腺癌

• 批准号: 8184046
• 负责人: JOO HA HWANG
• 金额: $ 61.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-14 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8184046
• 关键词: Accounting; Acoustics; Animal Model; Area; Autologous Transplantation; Cancer Etiology; Caring; Cessation of life; Clinical; Clinical Trials; Data; Desmoplastic; Devices; Diagnosis; Diffusion; Drug Delivery Systems; Environment; Exposure to; Focused Ultrasound Therapy; Human; Length; Malignant Neoplasms; Malignant neoplasm of pancreas; Modeling; Mus; Patients; Penetration; Pharmaceutical Preparations; Physiologic pulse; Research; Science; Survival Rate; Technology; Therapeutic Agents; Time; Tissues; Translating; Translations; Ultrasonography; United States; Vascular Permeabilities; Xenograft procedure; cancer statistics; chemotherapeutic agent; effective therapy; gemcitabine; human disease; improved; in vivo; innovation; mortality; mouse model; pancreatic neoplasm; radiation effect; response; standard of care; tumor

DESCRIPTION (provided by applicant): Pancreatic cancer accounts for 5% of cancer deaths in the United States and is the fourth leading cause of cancer mortality. According to the SEER Cancer Statistics Review, it is estimated that in 2009 there will have been over 42,000 new cases of pancreatic cancer and over 35,000 deaths. Current treatment options are of limited benefit with a 5-year survival rate following diagnosis of less than 5%. The current standard-of-care therapy, gemcitabine, only improves survival by a few weeks. It is clear that more effective therapy for the treatment of pancreatic cancer is needed. Ultrasound-enhanced drug delivery is an active and promising area of research. Ultrasound has been demonstrated to enhance vascular permeability and drug penetration into tissue, primarily due to mechanisms related to cavitation. Ongoing research efforts (including preliminary data from our lab presented in this proposal) have identified ultrasound mechanism and parameters that are likely to be effective in vivo. Several in vivo studies have been performed in various xenograft and syngenic autograft animal models that have demonstrated that ultrasound enhanced drug delivery is effective in decreasing tumor size and increasing survival duration; however, these tumor models, especially for pancreatic cancer, have been criticized for being unrealistic and not representative of the true in vivo environment seen in the human disease. In this proposal, we believe that we have developed a study that includes rigorous fundamental science, but also is rapidly translatable. The attractiveness of the strategy in this proposal is that it utilizes a chemotherapeutic agent that is the current standard of care (gemcitabine) along with focused ultrasound technology that is currently available and readily implementable to rapidly translate these results into human clinical trials. In addition, it brings for the first time to the study of ultrasound-enhanced drug delivery a unique and realistic animal model (KPC mice), which will provide much more realistic data to evaluate the potential for clinical translation. The overall aim of this proposal is to investigate whether ultrasound can enhance targeted drug penetration into an in vivo pancreatic tumor and improve survival duration. We believe that the successful accomplishment of the specific aims of this proposal will be a major step toward applying this promising approach to human patients who are suffering from pancreatic cancer. PUBLIC HEALTH RELEVANCE: Pancreatic cancer accounts for 5% of cancer deaths in the United States and is the fourth leading cause of cancer mortality and current treatments are essentially ineffective. The overall aim of this proposal is to investigate whether ultrasound can enhance targeted drug penetration into an in vivo pancreatic tumor and improve survival duration. We believe that the successful accomplishment of the specific aims of this proposal will be a major step toward applying this promising approach to human patients who are suffering from pancreatic cancer.

描述（由申请人提供）：胰腺癌占美国癌症死亡的5％，是癌症死亡率的第四个主要原因。根据《 SEER癌症统计评论》，据估计，在2009年，将有超过42,000例新的胰腺癌病例和35,000多人死亡。诊断少于5％后，目前的治疗选择的收益有限，生存率为5年。当前的护理标准疗法吉西他滨只能改善几周的生存。显然，需要更有效的治疗胰腺癌。 超声增强的药物输送是一个积极且有希望的研究领域。已证明超声可以增强血管通透性和药物渗透到组织中，这主要是由于与气蚀有关的机制。正在进行的研究工作（包括本提案中介绍的我们实验室的初步数据）已经确定了可能在体内有效的超声机制和参数。在各种异种移植和合成自体移植动物模型中已经进行了几项体内研究，这些动物模型表明超声增强的药物递送可有效降低肿瘤大小和增加的生存持续时间。然而，这些肿瘤模型，尤其是针对胰腺癌，因不现实而不是代表人类疾病中的真实体内环境而受到批评。 在该提案中，我们认为我们已经开发了一项研究，其中包括严格的基本科学，但也可以迅速翻译。该提案中该策略的吸引力在于，它利用了当前护理标准（吉西他滨）的化学治疗剂以及重点的超声技术，该技术目前可用且易于实现，可以快速将这些结果迅速转化为人类临床试验。此外，它首次将超声增强药物输送的研究带来了独特而逼真的动物模型（KPC小鼠），该模型将提供更现实的数据来评估临床翻译的潜力。该提案的总体目的是研究超声是否可以增强靶向药物渗透到体内胰腺肿瘤中并提高生存持续时间。我们认为，该提案的特定目标的成功完成将是将这种有前途的方法应用于患有胰腺癌的人类患者的重要一步。 公共卫生相关性：胰腺癌占美国癌症死亡的5％，是癌症死亡率的第四个主要原因，当前治疗本质上是无效的。该提案的总体目的是研究超声是否可以增强靶向药物渗透到体内胰腺肿瘤中并提高生存持续时间。我们认为，该提案的特定目标的成功完成将是将这种有前途的方法应用于患有胰腺癌的人类患者的重要一步。