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IMPACT OF CO-INHIBITION OF TGLI1 AND GP130 ON BREAST CANCER METASTASIS

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title
IMPACT OF CO-INHIBITION OF TGLI1 AND GP130 ON BREAST CANCER METASTASIS
author
Manore, Sara
abstract
Breast cancer is the most diagnosed cancer in American women and second cause of cancer-related deaths. HER2 amplification occurs in 10-15% of breast cancers and is associated with unfavorable prognoses. Triple-negative breast cancer (TNBC) comprises 15-20% of breast cancers and has limited treatment options. HER2-enriched and TNBC maintain the highest propensity to metastasize, which constitutes 90% of breast cancer mortality underscoring the need for novel combinatorial therapeutics. Truncated glioma-associated oncogene homolog 1 (tGLI1), an alternatively spliced GLI1, is a tumor-specific transcription factor. TGLI1 promotes stemness, preferential brain metastasis, and undergoes protein-protein interactions with signal transducer and activator of transcription 3 (STAT3) to mediate aggressive phenotypes in HER2-enriched and TNBC. Interleukin-6/interleukin-6 receptor/glycoprotein (IL-6/IL-6R/GP130) is the primary upstream regulator of STAT3 and is hyperactivated in breast cancer. Here we aim to investigate dual-inhibition of tGLI1 and IL-6/IL-6R/GP130 as a novel treatment modality for metastatic HER2-enriched and TNBC through repurposing FDA-approved compounds and the characterization of small molecule inhibitors.
subject
breast cancer
breast cancer stem cells
combination therapy
GP130
tGLI1
contributor
Lo, Hui-Wen (advisor)
Kucera, Gregory (committee member)
Hollis, Thomas (committee member)
Miller, Lance (committee member)
Reeves, Tony (committee member)
Smalley, Terrence (committee member)
date
2024-05-23T08:36:22Z (accessioned)
2024 (issued)
degree
Cancer Biology (discipline)
embargo
2026-05-22 (terms)
2026-05-22 (liftdate)
identifier
http://hdl.handle.net/10339/109447 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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