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

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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