Hs-27, a Novel Hsp90 Inhibitor, Exhibits Diagnostic and Therapeutic Potential in Triple Negative Breast Cancer

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2016-04-22

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Ramanujam, Nirmala

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Abstract

Heat-shock protein 90 (Hsp90) is a molecular chaperone that is ubiquitously expressed in all cell types and essential for maintaining cell homeostasis by assisting in protein folding, de-aggregation, and degradation. Hsp90 is upregulated in all breast tumors, where it is present on the cell surface, unlike in normal cells, and supports signal transduction pathways important for tumor progression. Hence, Hsp90 has emerged as an attractive anti-cancer target. Triple negative breast cancer (TNBC) is a highly aggressive and difficult to treat subtype of breast cancer. Because TNBC is unresponsive to hormone therapies, there are no good therapy options available. Thus, Hsp90 may serve as a reasonable target for TNBC. Hs-27 is a novel Hsp90 inhibitor made by Dr. Timothy Haystead of Duke University’s Department of Pharmacology and Cancer Biology. It was developed with a fluorescein contrast agent, which makes it suitable for diagnostics. Preliminary experiments with Hs-27 with breast cancer cell lines of different receptor subtypes show that it binds to ectopically expressed Hsp90 in tumor cells. In vitro therapy experiments also show that Hs-27 down-regulates client proteins implicated in tumor growth. In this study, I further establish Hs-27’s diagnostic and therapeutic ability in vivo through hyperspectral and fluorescence imaging in dorsal skinfold window chamber tumor models in mice. Largely, I observed that at lower doses, Hs-27 allows for real-time, non-invasive imaging for cancer detection and at higher doses has the potential for therapeutic benefits.

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Belonwu, Stella (2016). Hs-27, a Novel Hsp90 Inhibitor, Exhibits Diagnostic and Therapeutic Potential in Triple Negative Breast Cancer. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/11837.


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