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

膳食补充剂作为去势抵抗性前列腺癌的辅助治疗

• 批准号: 8834755
• 负责人: DAQING WU
• 金额: $ 16.1万
• 依托单位: METCURE THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834755
• 关键词: Acute; American Cancer Society; Androgen Receptor; Androgens; Animal Model; Animals; Apoptosis; Apoptotic; Biological Markers; CWR22Rv1; Cancer Patient; Castration; Cells; Clinical; Clinical Data; Clinical Research; Clinical Trials; Diagnosis; Dietary Formulations; Disease; Disease Resistance; Dose; Drug Formulations; Drug Kinetics; Excretory function; Exhibits; Feedback; Flavonoids; Fruit; Future; Gene Targeting; Generations; Genetic Transcription; Glycogen Synthase Kinase 3; Grant; Growth; Healthcare; Heat-Shock Proteins 90; Intravenous; Investigation; Legal patent; Malignant Neoplasms; Malignant neoplasm of prostate; Metabolism; Modeling; Molecular; Molecular Chaperones; Morbidity - disease rate; Mus; No-Observed-Adverse-Effect Level; Nude Mice; Oral; Outcome; Pathway interactions; Patients; Phase; Pomegranate; Pre-Clinical Model; Preparation; Receptor Signaling; Route; Signal Transduction; Small Business Technology Transfer Research; Solid; Sprague-Dawley Rats; Surrogate Endpoint; TCF Transcription Factor; Testing; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; Ubiquitination; United States; VCaP; absorption; castration resistant prostate cancer; clinical efficacy; cost effective; cytotoxicity; deprivation; dietary supplements; hormone therapy; improved; in vivo; mortality; mouse model; novel; pre-clinical; prostate cancer cell; prostate cancer cell line; public health relevance; receptor; response; subcutaneous; therapy resistant; tumor

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.

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。

项目成果

Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer.

• DOI: 10.1158/1535-7163.mct-17-1176
• 发表时间: 2018-09
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Yang Y;Mamouni K;Li X;Chen Y;Kavuri S;Du Y;Fu H;Kucuk O;Wu D
• 通讯作者: Wu D

A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models.

• DOI: 10.1016/j.neo.2018.06.003
• 发表时间: 2018-08
• 期刊: Neoplasia (New York, N.Y.)
• 作者: Mamouni K;Zhang S;Li X;Chen Y;Yang Y;Kim J;Bartlett MG;Coleman IM;Nelson PS;Kucuk O;Wu D
• 通讯作者: Wu D

Sensitive liquid chromatography/tandem mass spectrometry method for the determination of two novel highly lipophilic anticancer drug candidates in rat plasma and tissues.

灵敏液相色谱/串联质谱法测定大鼠血浆和组织中两种新型高亲脂性抗癌药物候选物。

• DOI: 10.1002/bmc.4064
• 发表时间: 2018
• 期刊: Biomedical chromatography : BMC
• 作者: Hooshfar,Shirin;Linzey,MichaelR;Wu,Daqing;Gera,Lajos;Mamouni,Kenza;Li,Xin;Chen,Yanhua;Yang,Yang;Olorunyolemi,Oluwasegun;Bartlett,MichaelG
• 通讯作者: Bartlett,MichaelG