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.

Public Health Relevance

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

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZCA1)
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Farrell, Dorothy F
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Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
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Hong, Bong Jin; Iscen, Aysenur; Chipre, Anthony J et al. (2018) Highly Stable, Ultrasmall Polymer-Grafted Nanobins (usPGNs) with Stimuli-Responsive Capability. J Phys Chem Lett 9:1133-1139
Malin, Dmitry; Petrovic, Vladimir; Strekalova, Elena et al. (2016) ?B-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target. Pharmacol Ther 160:1-10
Zhang, Yilin; Sriraman, Shravan Kumar; Kenny, Hilary A et al. (2016) Reversal of Chemoresistance in Ovarian Cancer by Co-Delivery of a P-Glycoprotein Inhibitor and Paclitaxel in a Liposomal Platform. Mol Cancer Ther 15:2282-2293
Ugolkov, Andrey; Gaisina, Irina; Zhang, Jin-San et al. (2016) GSK-3 inhibition overcomes chemoresistance in human breast cancer. Cancer Lett 380:384-92
Hong, Bong Jin; Cho, Vincent Y; Bleher, Reiner et al. (2015) Enhancing DNA-Mediated Assemblies of Supramolecular Cage Dimers through Tuning Core Flexibility and DNA Length--A Combined Experimental-Modeling Study. J Am Chem Soc 137:13381-8
Beauchamp, Elspeth M; Kosciuczuk, Ewa M; Serrano, Ruth et al. (2015) Direct binding of arsenic trioxide to AMPK and generation of inhibitory effects on acute myeloid leukemia precursors. Mol Cancer Ther 14:202-12
Sethi, Pallavi; Jyoti, Amar; Swindell, Elden P et al. (2015) 3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation. Nanomedicine 11:2013-23
Bondarenko, Gennadiy; Ugolkov, Andrey; Rohan, Stephen et al. (2015) Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors. Neoplasia 17:735-741
Xu, Xiang; Cai, Yuan; Wei, Ying et al. (2014) Identification of a new epitope in uPAR as a target for the cancer therapeutic monoclonal antibody ATN-658, a structural homolog of the uPAR binding integrin CD11b (?M). PLoS One 9:e85349
Lee, Kristy; Hart, Matthew R; Briehl, Margaret M et al. (2014) The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma. Int J Oncol 45:439-47

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