Sideport Needle Array Technologies for Prioritizing Drugs for Cancer Patients

描述(申请人提供)：超过90%的参加第一阶段或第二阶段临床试验的癌症患者没有从实验疗法中受益，但面临着药物毒性和其他与治疗有关的挑战。50多年来，医生一直使用患者特定的关于耐药性和敏感性的信息来为感染患者选择抗生素，但这种个性化的方法一直回避肿瘤界，因为在大多数情况下，体外药物敏感性分析中的癌细胞行为与体内治疗反应无关。我们已经开发了能够在手术切除肿瘤前几天在体内对多种药物或药物组合进行肿瘤学药物敏感性/耐药性测试的技术。这种方法允许药物与癌细胞相互作用，而后者处于天然的肿瘤微环境中。我们广泛的长期目标是为许多类型的实体肿瘤患者开发可靠的体内肿瘤学药物敏感性/耐药性分析。我们STTR第一阶段和第二阶段项目的总体目标是开发和测试适合人类淋巴瘤患者的设备，并启动人类临床试验。我们第一阶段的具体目标是开发一种一次性(一次性)多孔针阵列，并证明它符合药物输送精度规格。如果在第一阶段达到量化里程碑，第二阶段将继续进行以下目标：目标1)开发一种适用于人类淋巴瘤患者的原型；以及目标2)进行试点“人类第一”临床试验。这项拟议工作的意义在于，它将减少癌症患者接触引起毒性但没有临床益处的药物的频率。商业化潜力在一份全面的商业计划中进行了描述。我们提供生物技术、生命科学和个性化医学领域中备受尊敬的人士的来信，以证明这项技术的商业潜力。 公共卫生相关性：项目说明据估计，2008年美国将诊断出约140万新的癌症病例。需要改进以患者为基础的疗效指标来确定癌症治疗的优先顺序的方法。我们建议开发一种设备，能够在体内比较多种药物或组合，而肿瘤微环境完好无损。这项研究的长期目标是为多种类型的实体肿瘤患者开发可靠的体内肿瘤学药物敏感性/耐药性检测方法。这项技术将减少癌症患者接触引起毒性但没有临床益处的药物的频率。这种个性化的治疗方法将改善患者的预后，并提高数百万癌症患者的护理质量。

DESCRIPTION (provided by applicant): Over 90% of cancer patients that enroll in Phase I or II clinical trials experience no benefit from the experimental therapies, yet are exposed to drug toxicity and other challenges related to treatment. For over 50 years, physicians have used patient-specific information about drug resistance and sensitivity to select antibiotics for patients with infections, but this personalized approach has evaded the oncology community because cancer cell behavior in vitro drug sensitivity assays does not correlate with in vivo response to therapy in most cases. We have developed technologies that enable oncology drug sensitivity/resistance testing of multiple drugs or drug combinations in vivo during the days prior to surgical resection of a tumor. This approach allows drugs to interact with cancer cells while the latter are in their native tumor microenvironment. Our broad long-term goal is to develop reliable in vivo-based oncology drug sensitivity/resistance assays for patients with many types of solid tumors. Our overall goal of the STTR Phase I and II projects are to develop and test devices that are suitable for human lymphoma patients and to initiate human clinical trials. Our Specific Aim for the Phase I portion is to develop a single use (disposable) porous needle array and demonstrate that it meets drug delivery precision specifications. Provided that quantitative milestones are met in Phase I, Phase II will proceed with the following Aims: Aim 1) To develop a prototype suitable for use in human lymphoma patients; and Aim 2) to conduct a pilot "first in humans" clinical trial. The significance of the proposed work is that it will reduce the frequency of cancer patients being exposed to drugs that cause toxicity but offer no clinical benefit. The commercialization potential is described in a comprehensive business plan. We provide letters from highly respected individuals in the biotechnology, life sciences and personalized medicine fields to attest to the commercial potential of this technology. PUBLIC HEALTH RELEVANCE: Project Narrative It is estimated that approximately 1.4 million new cases of cancer will be diagnosed in the United States in 2008. Improved methods for prioritizing cancer therapeutics based on patient-based indicators of efficacy are needed. We are proposing to develop a device which enables comparison of multiple drugs or combinations in vivo, with the tumor micro-environment intact. The long-term goal of this research is to develop reliable in vivo- based oncology drug sensitivity/resistance assays for patients with many types of solid tumors. This technology will reduce the frequency of cancer patients being exposed to drugs that cause toxicity but offer no clinical benefit. This personalized treatment approach will improve patient outcome and enhance the quality of care for millions of individuals that suffer from cancer.