Carey K. Anders, MD, an Assistant Professor of Medicine, Division of Hematology-Oncology at the University of North Carolina (UNC), is a medical oncologist with a solid training and background in clinical-translational research methodology and a proven commitment to applying these methods to the study of breast cancer, particularly brain metastases. The candidate's long-term career goal is to become an independently-funded physician-scientist with a diverse portfolio including clinical trial design, preclinical modeling, and pharmacologic studies related to breast cancer brain metastases. In particular, the candidate will design and execute clinical trials testing novel agents to treat patients with breast cancer brain metastases, in particular aggressive triple-negative disease. In parallel, she will conduct pharmacologic disposition and efficacy studies in a preclinical intracranial triple-negative breast cancer model, results which will be seamlessly translated into future clinical trials. The candidate's short-term career goals fostered by this career development award are 1) to enhance her skills in clinical trial design, implementation and execution, 2) to expand her clinical trials skills to multi-center trial coordination, 3) to gain proficiency in clinical trial data analysis and interpretation, 4) to refine her ability to conduct preclinical pharmacologic disposition and efficacy studies, 5) to attain skills in analytic pharmacology technique and interpretation, and 6) to foster the development of professional skills and collaborations to lead a multidisciplinary research team. The proposed research plan, career development activities, mentoring team, and institutional environment are well-suited to assure the applicant achieves her goals. The research plan is built around the central hypothesis that PARP inhibition will prove efficacious in the treatment of aggressive triple-negative breast cancer brain metastases, a disease for which systemic therapeutic options are limited. To test the hypothesis, a parallel clinical/pre-clinical approach will be employed.
In Aim 1, the efficacy and safety of PARP inhibition, in combination with a chemotherapeutic active in breast cancer and known to traverse the blood brain barrier, to treat patients with triple-negative breast cancer brain metastases will be tested in a phase II, multi-center clinical trial. Nanoparticle formulations of anti-cancer agents enhance central nervous system delivery and are promising partners to couple with PARP inhibitors. Thus, Aims 2 and 3 are preclinical in nature and will test PARP inhibition in combination with several nanoparticle anti-cancer agents in an intracranial triple-negative breast cancer murine model. The candidate has assembled a mentorship team of internationally-recognized, independently-funded investigators with expertise in clinical/translational trial design (Carey), breast cancer biology (Carey, Perou), preclinical modeling (Perou, Sharpless, Miller) and nanoparticle pharmacology (Zamboni, Li, DiSimone) who will guide the candidate's research training and professional development in the collegial, productive and collaborative research environment of the SPORE-funded UNC Lineberger Comprehensive Cancer Center.

Public Health Relevance

Brain metastases arising from triple-negative breast cancer are a burgeoning clinical problem associated with poor prognosis and limited systemic therapeutic options. Inhibitors of Poly (ADP-Ribose) Polymerase (PARP) have proven efficacious in the treatment of extracranial triple-negative breast cancer and cross the blood brain barrier. This proposal will test the efficacy of PARP inhibitors to treat triple-negative breast cancer brain metastases in a multi-center, phase II trial (Aim 1) and pre-clinically, in combination with nanoparticle anticancer agents, in an intracranial triple-negative breast cancer murine model (Aims 2 - 3) with the ultimate goal of improving outcomes for patients diagnosed with this aggressive disease.

Agency
National Institute of Health (NIH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23CA157728-04
Application #
8718776
Study Section
Subcommittee B - Comprehensiveness (NCI)
Program Officer
Lim, Susan E
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
McKee, Megan J; Keith, Kevin; Deal, Allison M et al. (2016) A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience. Oncologist 21:16-20
Keith, Kevin C; Lee, Yueh; Ewend, Matthew G et al. (2016) ACTIVITY OF TRASTUZUMAB-EMTANSINE (TDM1) IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A CASE SERIES. Cancer Treat Commun 7:43-46
Sambade, Maria; Deal, Allison; Schorzman, Allison et al. (2016) Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT(®) nanoparticle formulation against non-small-cell lung cancer brain metastases. Nanomedicine (Lond) 11:1947-55
Franceschi, Ana Marija; Moschos, Stergios J; Anders, Carey K et al. (2016) Use of Susceptibility-Weighted Imaging (SWI) in the Detection of Brain Hemorrhagic Metastases from Breast Cancer and Melanoma. J Comput Assist Tomogr 40:803-5
Karginova, Olga; Siegel, Marni B; Van Swearingen, Amanda E D et al. (2015) Efficacy of Carboplatin Alone and in Combination with ABT888 in Intracranial Murine Models of BRCA-Mutated and BRCA-Wild-Type Triple-Negative Breast Cancer. Mol Cancer Ther 14:920-30
Family, Leila; Bensen, Jeannette T; Troester, Melissa A et al. (2015) Single-nucleotide polymorphisms in DNA bypass polymerase genes and association with breast cancer and breast cancer subtypes among African Americans and Whites. Breast Cancer Res Treat 149:181-90
Johnson, Rebecca H; Hu, Pingzhao; Fan, Cheng et al. (2015) Gene expression in "young adult type" breast cancer: a retrospective analysis. Oncotarget 6:13688-702
Tichy, J R; Deal, A M; Anders, C K et al. (2015) Race, response to chemotherapy, and outcome within clinical breast cancer subtypes. Breast Cancer Res Treat 150:667-74
Siegel, Marni B; Van Swearingen, Amanda E D; Anders, Carey K (2014) Approaches for optimal drug development and clinical trial design for breast cancer brain metastasis. Oncology (Williston Park) 28:579, 584-5
Malin, Dmitry; Strekalova, Elena; Petrovic, Vladimir et al. (2014) *B-crystallin: a novel regulator of breast cancer metastasis to the brain. Clin Cancer Res 20:56-67

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