Hs-27, a Novel Hsp90 Inhibitor, Exhibits Diagnostic and Therapeutic Potential in Triple Negative Breast Cancer
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.
Type
Honors thesisDepartment
BiologyPermalink
https://hdl.handle.net/10161/11837Citation
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.Collections
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