Prostate cancer is the mostly commonly diagnosed non-cutaneous malignancy and the second leading cause of cancer-related death affecting men in the United States. Moreover, it disproportionately affects the men of African origin, who exhibit significantly greater incidence and mortality as compared to the men of European origin. Since androgens play an important role in the growth of normal prostate and prostate tumors, targeting of androgen signaling has remained a mainstay for the treatment of aggressive prostate cancer. Over the years, multiple approaches have been evaluated to effectively target the androgen signaling pathway that include direct targeting of the androgens, androgen receptor (AR), AR co-regulators or other alternate mechanisms that impact the outcome of androgen signaling. Several of these approaches are currently in clinical practice, while some are still pending further development and clinical evaluation. This remarkable progress has resulted from extensive laboratory, pre-clinical and clinical efforts, and mechanistic learnings from the therapeutic success and failures. In this review, we describe the importance of androgen signaling in prostate cancer biology and advances made over the years to effectively target this signaling pathway. We also discuss emerging data on the resistance pathways associated with the failure of various androgen signaling- targeted therapies and potential of this knowledge for translation into future therapies for prostate cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy, which disproportionately affects African American (AA) women. Lack of awareness and socioeconomic factors are considered important players in OC racial health disparity, while at the same time, some recent studies have brought focus on the genetic basis of disparity as well. Differential polymorphisms, mutations and expressions of genes have been reported in OC patients of diverse racial and ethnic backgrounds. Combined, it appears that neither genetic nor the socioeconomic factors alone might explain the observed racially disparate health outcomes among OC patients. Rather, a more logical explanation would be the one that takes into consideration the combination and/or the interplay of these factors, perhaps even including some environmental ones. Hence, in this article, we attempt to review the available information on OC racial health disparity, and provide an overview of socioeconomic, environmental and genetic factors, as well as the epigenetic changes that can act as a liaison between the three. A better understanding of these underlying causes will help further research on effective cancer management among diverse patient population and ultimately narrow health disparity gaps.

E23253 Background: Acquired resistance to available chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Exosomes, small (50-150 nm) secreted membrane-enclosed vesicles containing functional biomolecules, are important mediator of intercellular communication and play pivotal role in various physiological and pathological functions. However, the role of exosomes in chemoresistance has not fully explored. Here, we explored the role of exosomes in promoting acquired resistance to Gemcitabine and Nab-paclitaxel in PDAC. Methods: Conditioned media from vehicle-treated (V-CM), gemcitabine-treated (Gem-CM), nab-paclitaxel-treated (P-CM) and gem/nab-paclitaxel-treated (G/P-CM) PDAC (MiaPaCa and Colo-357) cells was collected and fractionated into soluble (Sol) and vesicular (EV) fractions. PDAC cells were pre-treated with Sol and EV fractions followed by treatment with various doses (0-80 μM) of gemcitabine, (0-100 nM) of nab-paclitaxel or both for different time intervals (48 and 72 h). EVs were separated by differential ultracentrifugation, size was determined using Dynamic Light Scattering (DLS) and assessed for their chemoresistance conferring activity in PDAC cells. Immunoblotting was performed to examine the specific markers associated with EVs. Results: Both Gem-CM and Gem-EV provided significant protection to gemcitabine-treated cells, while Gem-Sol had only negligible effect. DLS based-size distribution analysis identified EVs of three different size viz. large ( > 1500 nm), medium (500-1500 nm) and small (100-300 nm). Treatment of large and medium sized Gem-EVs did not show any chemoprotective effect in PDAC cells, while smaller Gem-EVs provided remarkable survival benefits to PDAC cells against gemcitabine treatment. Immunoblot data revealed that these active EVs are enriched with CD9 and CD63, specific markers of exosomes. Conclusions: Gemcitabine induces secretion of exosomes in PDAC cells and promoted acquired resistance. Studies are ongoing for Nab-paclitaxel-treated (P-CM) and Gem/Nab-paclitaxel-treated (G/P-CM) and will be reported in the meeting.