A Dietary Supplement As Adjunct Therapy In Castration-Resistant Prostate Cancer

描述（由申请人提供）：去势抵抗性前列腺癌去势抵抗性前列腺癌（CRPC）直接导致患者死亡。因此，迫切需要开发新的有效的辅助治疗，以提高CRPC对激素治疗的反应。最近，我们开发了ProFineTM，这是一种专有配方，由石榴果实中富含的生物活性黄酮组成，并在CRPC细胞中证明了其有效的抗癌活性。在这项I期STTR申请中，我们假设ProFineTM有效地共同靶向AR和Akt信号传导，从而激活CRPC细胞的凋亡并使其对雄激素剥夺治疗（ADT）敏感。提出了两个目标：目的1将确定ProFineTM在CRPC细胞中的作用机制，特别是ProFineTM如何抑制雄激素受体信号传导;目的2将评价ProFineTM在CRPC原位模型中增强Enzalutamide激素治疗的疗效。这些研究的完成将为未来的专利申请和第二阶段STTR申请提供坚实的证据。

DESCRIPTION (provided by applicant): Castration-Resistant Prostate Cancer Castration-resistant prostate cancer (CRPC) directly contributes to patient mortality. It is imperative to develop new and effective adjunct therapy to enhance the response of CRPC to hormonal therapy. Recently we developed ProFineTM, a proprietary formula consisting of bioactive flavonoids enriched in pomegranate fruit, and demonstrated its potent anti-cancer activity in CRPC cells. In this Phase I STTR application, we hypothesize that ProFineTM potently co-targets AR and Akt signaling, thereby activating apoptosis in CRPC cells and sensitizing them to androgen deprivation therapy (ADT). Two Aims are proposed: Aim 1 will determine the mechanism of action of ProFineTM in CRPC cells, specifically how ProFineTM inhibits androgen receptor signaling; Aim 2 will evaluate the efficacy of ProFineTM in enhancing enzalutamide hormonal therapy in an orthotopic model of CRPC. Accomplishment of the proposed studies will provide solid evidence for future patent application and a Phase II STTR application.