Tumor Targeted Nanobins for the Treatment of Metastatic Breast and Ovarian Cancer

描述（由申请人提供）：转移性三阴性乳腺癌和卵巢癌是目前缺乏有效治疗的致命疾病。最近开发的活性药物的纳米颗粒形式，封装在脂质和聚合物试剂中，已经导致称为纳米仓的平台。先导剂提供了经验证的化疗剂的显著增加的功效和安全性。这些纳米仓已被证明能够安全地向肿瘤提供有效的一线抗癌药物，如三氧化二砷，其疗效比母体药物更高，从而导致显著更高的治疗指数。这种纳米技术平台的既定功效来自被动的、基于EPR和基于表位的分子靶向策略。一个由化学家、肿瘤生物学家、材料科学家、妇科肿瘤学家和转化科学家组成的跨学科团队将把主要药物推向临床。同时，他们将开发新的纳米酶制剂，将其他有效的抗癌药物（如顺铂）与靶向肿瘤特异性表位的表面束缚抗体结合起来。所提出的药剂还将能够向实体瘤递送多种敏化剂和细胞毒性剂。这些药物将在实验矩阵中进行筛选，该实验矩阵包括定量里程碑和在几种乳腺癌和卵巢癌原位异种移植动物模型中对纳米箱的评价。这个跨学科的团队将继续与NCI癌症纳米技术联盟的成员合作，在这些罕见的妇科和转移性乳腺癌的动物模型中评估其他机构的新兴平台。该平台合作伙伴关系的研究工作将进一步加强和协调，由一名团队成员负责推进药物从发现阶段到IND申请和概念验证阶段2试验的专业知识，这些研究的预期成果将是开发安全有效的纳米材料，用于治疗这些目前无法治愈的癌症。相关性（见说明）：癌症仍然是对数百万人健康的重大健康挑战。需要开发广泛创新的非传统癌症治疗干预措施，以加快进展。该应用将导致临床上有用的抗癌药物候选物和基于纳米颗粒的药物的转化管道。这些药物代表了治疗罕见和难以治疗的癌症（如卵巢癌和转移性乳腺癌）的药物递送新范式

DESCRIPTION (provided by applicant): Metastatic Triple negative breast cancer and ovarian cancer are lethal diseases that currently lack effective treatments. Recently developed nanoparticulate forms of active drugs, encapsulated in lipid and polymeric agents, have led to a platform known as nanobins. The lead agents provide dramatically increased efficacy and safety of validated chemotherapeutic agents. The proven ability of these nanobins to safely deliver potent, front line anticancer drugs, such as arsenic trioxide, to tumors with greater efficacy than the parent drugs results in a significantly higher therapeutic index. The established efficacy of this nanotechnology platform arises from both passive, EPR-based and epitope-based molecular targeting strategies. An interdisciplinary team of chemists, tumor biologists, materials scientists, gynecological oncologists, and translational scientists will advance the lead agents to the clinic. In parallel, they will develop new nanobin agents that combine other potent anticancer drugs, such as Cisplatin, with surface tethered antibodies that target tumor specific epitopes. The proposed agents will be also able to deliver multiple sensitizing and cytotoxic agents to solid tumors. The agents will be screened in an experimental matrix that includes quantitative milestones and evaluation of nanobins in several orthotopic xenograph animal models of breast and ovarian cancer. This interdisciplinary team will continue to collaborate with members of the NCI Alliance for Nanotechnology in Cancer to evaluate emerging platforms from other institutions in these animal models of rare gynecological and metastatic breast cancers. The research efforts of this Platform Partnership will be further augmented and coordinated by a team member with expertise in advancing drugs from the discovery stage to IND filings and to proof of concept phase 2 trials The anticipated outcome of these studies will be the development of safe and effective nanomaterials for the treatment of these currently incurable cancers. RELEVANCE (See instructions): Cancer continues to represent a significant health challenge to the well being of millions of people. Broadly innovative non-traditional therapeutic interventions for the treatment of cancer need to be developed in order to accelerate progress. This application will lead to clinically useful anti-cancer drug candidates and a translational pipeline of nanoparticle based drugs. These agents represent a new paradigm in drug delivery for the treatment of rare and difficult to treat cancers such as ovarian and metastatic breast cancer