Item Details

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