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You searched for +publisher:"University of North Carolina" +contributor:("Maxfield, Kimberly"). One record found.

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University of North Carolina

1. Maxfield, Kimberly. Genetic Dissection of Therapeutic Intervention Targets in Triple Negative Breast Cancer.

Degree: Pharmacology, 2015, University of North Carolina

Triple negative breast cancer (TNBC) is the most aggressive and metastatic type of breast cancer, accounting for 20% of all breast cancer diagnoses. Currently, there are no TNBC-specific targeted therapies in the clinic and therefore, broad-spectrum cytotoxic chemotherapeutic regimens remain the standard of care. Due to high rates of innate drug resistance, many TNBC patients do not respond to these regimens and, therefore, have no other therapeutic options. Our group employed a pan-genomic loss of function screen to systematically dissect the molecular architecture that functionally supports TNBC to uncover new therapeutic entry points. We further applied a paclitaxel-based synthetic lethal approach to increase our discovery space to also identify those molecular components that modulate chemoresponsiveness. To encompass the heterogeneity found within the TNBC patient population, we screened four triple negative tumor-derived breast cancer cell lines that represent the spectrum of TNBC oncogenic aberrations and chemoresponse profiles. We also accounted for the two molecular subtypes, claudin-low and basal-like that comprise the majority of TNBC cases. These screens revealed a number of core modulators of tumor cell viability and paclitaxel-induced cellular stress that have not been previously appreciated for supporting TNBC biology at the cell autonomous level. In particular, this strategy implicated the signaling supported by the cytokine receptor, CXCR3, and its ligand, CXCL9, to promote mitotic fidelity and tumor cell survival in the basal-like TNBC molecular subtype. In addition, we uncovered a requirement for the AMPK family member, SIK2, as a key nutrient sensor that may inhibit excessive autophagy. Inhibition of SIK2 enhanced autophagic flux and a loss of cell viability in a variety of TNBC genetic backgrounds. Finally, we discovered that cancer testes antigen transcription factor, ZNF165, directly repressed expression of negative TGFβ regulators thereby specifying a pro-tumorigenic TGFβ gene expression profile. Given that the expression of ZNF165 is otherwise restricted to the male testes, ZNF165 may represent a mechanism by which tumors engage anomaly-expressed proteins to promote survival. Taken together, our screening approach uncovered novel TNBC tumor cell vulnerabilities that identified cellular processes that could lead to new therapeutic approaches. Advisors/Committee Members: Maxfield, Kimberly, Whitehurst, Angelique, Sondek, John, Johnson, Gary, McLeod, Howard L., Baldwin, Albert, Perou, Charles.

Subjects/Keywords: Pharmacology; Biology; School of Medicine; Department of Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Maxfield, K. (2015). Genetic Dissection of Therapeutic Intervention Targets in Triple Negative Breast Cancer. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:318b1399-81a7-4737-b0c7-96f242284420

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Maxfield, Kimberly. “Genetic Dissection of Therapeutic Intervention Targets in Triple Negative Breast Cancer.” 2015. Thesis, University of North Carolina. Accessed September 23, 2020. https://cdr.lib.unc.edu/record/uuid:318b1399-81a7-4737-b0c7-96f242284420.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Maxfield, Kimberly. “Genetic Dissection of Therapeutic Intervention Targets in Triple Negative Breast Cancer.” 2015. Web. 23 Sep 2020.

Vancouver:

Maxfield K. Genetic Dissection of Therapeutic Intervention Targets in Triple Negative Breast Cancer. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2020 Sep 23]. Available from: https://cdr.lib.unc.edu/record/uuid:318b1399-81a7-4737-b0c7-96f242284420.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Maxfield K. Genetic Dissection of Therapeutic Intervention Targets in Triple Negative Breast Cancer. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:318b1399-81a7-4737-b0c7-96f242284420

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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