Ultrasound enhanced penetration for treatment of pancreatic cancer

超声增强穿透治疗胰腺癌

• 批准号: 8332761
• 负责人: JOO HA HWANG
• 金额: $ 52.69万
• 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/8332761
• 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.

描述（由申请人提供）：在美国，胰腺癌占癌症死亡的 5%，是第四大癌症死亡原因。根据 SEER 癌症统计回顾，估计 2009 年将有超过 42,000 例新发胰腺癌病例，超过 35,000 例死亡。目前的治疗方案效果有限，诊断后 5 年生存率低于 5%。目前的标准治疗方法吉西他滨只能将生存期提高几周。显然，需要更有效的疗法来治疗胰腺癌。 超声增强药物输送是一个活跃且有前途的研究领域。超声波已被证明可以增强血管通透性和药物对组织的渗透，这主要是由于与空化相关的机制。正在进行的研究工作（包括本提案中提供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。在各种异种移植和同基因自体移植动物模型中进行了几项体内研究，这些研究表明超声增强的药物输送可有效减小肿瘤大小并延长生存时间；然而，这些肿瘤模型，特别是胰腺癌模型，被批评为不切实际且不能代表人类疾病中真实的体内环境。 在这项提案中，我们相信我们已经开展了一项研究，其中包括严格的基础科学，而且可以快速转化。该提案中该策略的吸引力在于，它利用了当前护理标准的化疗药物（吉西他滨）以及目前可用且易于实施的聚焦超声技术，以将这些结果快速转化为人体临床试验。此外，它首次为超声增强药物输送的研究带来了独特且真实的动物模型（KPC小鼠），这将为评估临床转化的潜力提供更真实的数据。该提案的总体目标是研究超声是否可以增强靶向药物对体内胰腺肿瘤的渗透并延长生存时间。我们相信，成功实现该提案的具体目标将是将这种有希望的方法应用于患有胰腺癌的人类患者迈出的重要一步。