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Dissertation/Thesis Abstract

Development of CAPER Peptides for the Treatment of Breast Cancer
by Chilewski, Shannon D., Ph.D., University of the Sciences in Philadelphia, 2020, 143; 27547515
Abstract (Summary)

Breast cancer is a leading cancer among women and is a major cause of death worldwide. While not just one disease, breast cancer encompasses many biologically different subtypes with distinct pathologies and clinical ramifications. In the case of estrogen receptor (ER) positive breast cancer, estrogens stimulate mammary epithelial cell proliferation and contribute to the development and progression of the disease. To treat ER-positive breast cancer patients, endocrine targeted therapies such as tamoxifen are commonly used. However, 40–50% of these patients do not respond or develop resistance to these therapies, and therefore additional treatment options are needed. In the case of triple negative breast cancer (TNBC), there is a lack of expression of the ER, progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) and this subtype has the poorest prognosis. There are currently very limited therapies available for TNBC, and due to the receptor status, endocrine therapies are ineffective. This leaves TNBC patients with chemotherapy and radiation as the only options, and therefore additional treatments are urgently needed.

CAPER is a coactivator of activating protein-1 (AP-1) (interacting specifically with the c-Jun component) and the ER and is known to be involved in human breast cancer pathogenesis. Not only has CAPER shown a role in ER-positive breast cancer but recent data has also demonstrated a role for CAPER in TNBC. In normal breast tissue, CAPER is not detectable or expressed at low levels. However, in both ER-positive and TNBC, CAPER exhibits a significantly higher level of expression. Additionally, it has been shown that when CAPER expression is reduced via knockdown cell proliferation is decreased in both in vitro and in vivo settings.

Due to CAPER’s role in both ER-positive and TNBC, disrupting the interaction of CAPER with the ER and/ or c-Jun could be a novel approach to treat breast cancer patients. The work described herein will review the development and in vitro testing of CAPER peptides to inhibit the coactivator activity of CAPER with c-Jun and/or the ER.

Indexing (document details)
Advisor: Jasmin, Jean-Francois
Commitee: Harvison, Peter, Haulenbeek, Jonathan, Wallach, Jason, Wang, Zhihong
School: University of the Sciences in Philadelphia
Department: Pharmacology & Toxicology
School Location: United States -- Pennsylvania
Source: DAI-B 81/5(E), Dissertation Abstracts International
Subjects: Pharmaceutical sciences, Oncology
Keywords: Breast cancer, Cancer, CAPER, Peptides, Rbm39
Publication Number: 27547515
ISBN: 9781392732519
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