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Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, Emily Ma

Dissertations

Breast cancer is the second leading cause of cancer-related deaths among women in the US. Histone modifications are common epigenetic changes that have been implicated in several breast cancers, including HER2+ breast cancers. Current therapies, such as trastuzumab, block the HER2 receptor to reduce tumor growth. Unfortunately, HER2+ breast cancers have found ways to overcome these therapies, leading to tumor resistance, metastases, and poor survival outcomes. A better understanding of the underlying mechanisms contributing to HER2+ breast cancer resistance may lead to the discovery of novel therapeutic strategies to improve patient outcomes.One prognostic marker for poor survival in women with …

Role Of Daxx As A Predictive Biomarker In Breast Cancer, Michelle Lucia Fernandez

Master's Theses

Breast cancer is the most commonly diagnosed form of cancer in women, besides skin cancer, and second only to lung cancer for cause of mortality. It is divided into three subtypes, depending on different molecular or pathologic characteristics, including estrogen or progesterone receptor-positive (ER/PR+), human epidermal growth factor receptor-2-positive (HER2+) and triple negative breast cancer (TNBC). There are several therapies used to target these subtypes, but there is still a chance that the cancer will recur into a more aggressive, resistant form even if the therapies were successful before. This recurrence is believed to be due to the Cancer Stem …

Daxx As A Restrictor Of Tumor Initiating Cell Survival In Er+ Breast Cancer And Its Therapeutic Implications, Daniel Seamus Peiffer

Dissertations

Breast cancer overall is the second most common cause of cancer related death in women, with one in eight women being diagnosed during their lifetime. Breast cancer itself is divided into subtypes based on the expression levels of the hormone receptors including the estrogen receptor (ER) and the progesterone receptor (PR), as well as expression of the growth factor receptor epidermal growth factor receptor 2 (HER2). ER+ breast cancer is the most common breast cancer diagnosis, and these tumors are defined as being initially dependent on activation of the receptor for growth. Based on this, targeted endocrine therapies (ETs) have …

The Role Of Notch-1-Mediated Repression Of Pten On Growth And Cancer Stem Cell Survival In Trastuzumab Resistant, Her2+ Breast Cancer, Andrew Thomas Baker

Dissertations

Trastuzumab targets the ErbB2 (HER2) receptor on breast cancer cells to attenuate HER2 driven tumor formation. Trastuzumab reduces both downstream PI3K/Akt and MAPK pathway signaling as well as the breast cancer stem cell (BCSC) population. BCSCs are hypothesized to be responsible for tumor recurrence, metastasis, as well as drug resistance. Today, resistance to trastuzumab remains a major clinical problem for women diagnosed with HER2+ breast cancer. Attenuation of PI3K/Akt and MAPK pathways may occur through the tumor suppressor, PTEN. Women with HER2+ breast tumors expressing less PTEN and increased PI3K/Akt or MAPK activity have worse overall outcome. Previously we have …

Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya

Dissertations

The ErbB-2 gene is amplified and the resulting protein product overexpressed in 15-30% of breast tumors, and associated with aggressive behavior and poor overall survival. Currently, there are two FDA approved therapies targeting ErbB-2 for the treatment of ErbB-2 positive breast cancer: trastuzumab, a humanized monoclonal antibody is directed against the extracellular domain of ErbB-2 and lapatinib, a dual EGFR/ErbB-2 tyrosine kinase inhibitor. Unfortunately, anti-ErbB-2 therapy resistance remains a major problem in metastatic breast cancer. Our data suggested that gene amplification or overexpression of ErbB-2 inhibits Notch-1 transcriptional activity and trastuzumab or lapatinib increased

Notch-1 transcriptional activity. Furthermore, Notch-1 is …