Browsing by Author "Karami, Samaneh"
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Item Androgen Receptor in Hormone Receptor-Positive Breast Cancer(2023-12-29) Khan, Ashfia Fatima; Karami, Samaneh; Peidl, Anthony S.; Waiters, Kacie D.; Babajide, Mariam Funmi; Bawa-Khalfe, TasneemBreast cancer subtypes expressing hormone receptors (HR+ BCa) have a good prognosis and respond to first-line endocrine therapy (ET). However, the majority of HR+ BCa patients exhibit intrinsic or acquired ET resistance (ET-R) and rapid onset of incurable metastatic BCa. With the failure of conventional ET, limited targeted therapy exists for ET-R HR+ BCa patients. The androgen receptor (AR) in HR-negative BCa subtypes is emerging as an attractive alternative target for therapy. The AR drives Luminal AR (LAR) triple-negative breast cancer progression, and LAR patients consistently exhibit positive clinical benefits with AR antagonists in clinical trials. In contrast, the function of the AR in HR+ BCa is more conflicting. AR in HR+ BCa correlates with a favorable prognosis, and yet, the AR supports the development of ET-R BCa. While AR antagonists were ineffective, ongoing clinical trials with a selective AR modulator have shown promise for HR+ BCa patients. To understand the incongruent actions of ARs in HR+ BCa, the current review discusses how the structure and post-translational modification impact AR function. Additionally, completed and ongoing clinical trials with FDA-approved AR-targeting agents for BCa are presented. Finally, we identify promising investigational small molecules and chimera drugs for future HR+ BCa therapy.Item Impact of SUMO Post-translational Modification on Breast Cancer Development(2023-04-13) Babajide, Funmi; Karami, Samaneh; Waiters, Kacie; Peidl, AnthonyProteins are subject to post-translational modifications (PTM) that ensure the plethora of unique cellular functions. SUMO-PTM allows proteins to maintain cellular homeostasis and respond to abnormal stressors. SUMO-PTM of proteins is a dynamic reversible process important to cellular biology and normal human physiology. Consistently an imbalance of SUMO-modified proteins (or SUMOylation) can lead to breast cancer development and support onset of metastatic disease. Hence, the long-term objective of our studies is to understand and develop appropriate therapeutics to restore SUMO-PTM balance in breast cancer. At a molecular level, the Small Ubiquitin-like Modifier (SUMO) molecule forms a covalent bond with lysine residues on target proteins with the work of SUMO-specific family of conjugating enzymes including SUMO E3 ligases. Inversely, SUMO-specific protease or deSUMOylase hydrolyze the bond between SUMO and the target protein to maintain the unmodified form of the substrate. Here, we examine protein interactions between novel SUMO E3 ligase and its target protein in breast cancer cells stressed with conventional anti-cancer therapy. Concurrently, we test how excessive SUMO-PTM impacts breast cancer development using a novel genetically engineered mouse model (GEMM). These results can aid in the further understanding of protein function and cellular homeostasis in context of breast cancer development and resistance to conventional anti-cancer therapy.