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Co-targeting oncogenic pathways in advanced prostate cancer

共同靶向晚期前列腺癌的致癌途径

基本信息

批准号：
9106639
负责人：
KAREN M CICHOWSKI
金额：
$ 38.12万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9106639
关键词：
Ablation American Androgen Receptor Androgens Automobile Driving Biochemical CDK2 gene Cancer Patient Castration Cell Cycle Cell Death Cell Proliferation Cessation of life ChIP-seq Clinical Clinical Trials Combined Modality Therapy Complex Data Development Diagnosis Disease Drug Combinations Drug Targeting EZH2 gene Early Diagnosis Enhancers Epigenetic Process Gene Silencing Genes Genetic Genomic approach Genomics Goals Growth In Vitro Individual Lead Lymphoma Malignant Neoplasms Malignant neoplasm of prostate Mediating Modeling Molecular Mutate Neoplasm Metastasis Oncogenes Oncogenic PPAR gamma PTEN gene Pathway interactions Patients Play Polycomb Process Refractory Reporting Resistance Role Signal Transduction Therapeutic Therapeutic Effect Translations Xenograft Model Xenograft procedure advanced disease castration resistant prostate cancer cell killing chemical genetics curative treatments defined contribution effective therapy histone methyltransferase in vivo inhibitor/antagonist insight killings men mortality novel overexpression pre-clinical preclinical study prostate cancer cell prostate cancer model public health relevance response screening targeted treatment treatment response tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer is the most frequently diagnosed non-dermatological malignancy in North American men. While screening and early detection have reduced mortality, there is still no curative treatment for advanced disease. As such all patients that develop castration-resistant tumors will ultimately die from their disease. Therefore developing an effective therapy for advanced prostate cancer represents an important unmet clinical need. By targeting two important oncogenic pathways we have identified a combination therapy that kills castration-resistant prostate cancer. Notably, while many (failed) targeted therapies have been shown to slow prostate cancer growth, this drug combination actually causes frank tumor regression in vivo in several models. The goal of this project is to deconstruct the mechanism by which these agents function, use this insight to identify the optimal drugs/targets, and validate the therapeutic effects of these agents in patient-derived xenograft (PDX) models. This will be accomplished through cellular, epigenetic, and genomic approaches and by conducting additional preclinical studies in vivo. These studies will not only provide invaluable preclinical data to guide the development of a clinical trial, but will uncover mechanisms that kill castration- resistant prostate cancer, which may ultimately lead to the development of additional therapeutic strategies.