Functional imaging gives clinicians the ability to monitor breast cancer progression and response to therapy. Modern techniques such as Positron Emission Tomography (PET) has allowed for clinicians to visualize the metabolic need of breast cancer and track it longitudinally. However, these techniques are expensive, technologically complex and not easily implemented in rural areas. To add to the difficulty, breast cancer is a highly heterogeneous disease. The heterogeneity means that a single therapy is not always applicable to all patients and every patient requires an individual treatment plan. Being able to first diagnose breast cancer, and then monitor its response to therapy in a cost-effective manner is imperative to improve the survival of patients with this disease.

Optical techniques such as fluorescence are ideal for these applications since they can be fast and implemented with portable technology. These techniques use differences in light interaction with tissue to allow for abnormality detection. This dissertation tests the hypothesis that the fluorescent molecularly specific agents, protoporphyrin IX (PpIX) and 2-NBDG, which utilize metabolic alterations caused by cancer, can be used for ubiquitous breast cancer differentiation and therapy monitoring. Confocal microscopy is used to demonstrate the applicability of both agents in vitro to breast cancer cells regardless of phenotype.

First...

The androgen receptor (AR) signaling axis is a well-established therapeutic target in prostate cancer, due to its central role in tumor maintenance and progression. Although patients respond initially to androgen deprivation therapies and AR antagonists, they invariably progress to a castration-resistant state. Consequently, there is an unmet need for agents that target the AR signaling axis in a unique manner.

Histone deacetylase (HDAC) inhibitors repress AR signaling and prostate cancer growth in cellular and xenograft models. However, HDAC inhibitors also induce epithelial to mesenchymal (EMT) and neuroendocrine differentiation, both of which are associated with prostate cancer progression and aggressiveness. Given that 18 different HDAC isoforms have been identified in humans, and non-selective or Class I (HDAC1, 2, 3, and 8) HDAC inhibitors have been used in most of these studies, the relative contribution of individual HDAC isoforms to AR transcriptional activity and prostate cancer pathophysiology remains to be elucidated. The overarching goals of this study were to (1) determine the role of individual Class I HDACs in AR transcriptional activity and prostate cancer growth, (2) identify selective HDAC inhibitors that have reduced adverse profiles to the treatment of prostate cancer...