Neuroendocrine prostate cancer (NEPC) is a currently incurable, lethal subtype of prostate cancer that can develop from the disease following prolonged hormonal therapy. Unfortunately, there are few treatment options available for NEPC and new therapeutic targets and more effective treatments are urgently needed to improve its management. A state-of-the-art pre-clinical model of NEPC, developed in our group, is giving us unprecedented levels of accuracy in monitoring how NEPC progresses. Using this model and advanced gene and gene expression analyses, we have observed that elevated expression of HP1a, a gene not previously reported to be involved NEPC, is correlated with NEPC development. In our pilot study, these findings were further validated in clinical samples. Furthermore, we also observed increased HP1a is an early event during NEPC development and a reduction in HP1a expression was found to lead to inhibition of cancer cell growth. These results suggest HP1a may play an important role in NEPC development. In the proposed study, we hypothesize that 1) HP1a impacts multiple aspects of cancer biology and is functionally important in NEPC development; 2) reduced HP1a expression in cancer cells will significantly suppress NEPC growth; and 3) reagent targeting HP1a can be used as a novel therapy to treat NEPC. The ultimate goals of this project are to have a better understanding of the function of HP1a in NEPC and to produce potential therapeutics designed to target HP1a and hence suppress NEPC development. When successful, this study will improve our understanding of mechanisms underlying the development of NEPC and also provide new insights for the personalized treatment strategy for prostate cancer patients. Identification of novel therapeutic agents in this study will lead to more effective therapy and better quality of life of prostate cancer patients.

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