Clinical genomic predictive model of first line androgen receptor inhibitor therapy outcomes in men with mCRPC

男性 mCRPC 一线雄激素受体抑制剂治疗结果的临床基因组预测模型

• 批准号: 10264941
• 负责人: Andrew J Armstrong
• 金额: $ 63.26万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264941
• 关键词: AR gene; Acetates; Alkaline Phosphatase; Androgen Antagonists; Androgen Receptor; Androgens; Biological Markers; Biology; Cancer Etiology; Castration; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Trials; Costs and Benefits; DNA Sequence Alteration; Data; Detection; Development; Disease; Eligibility Determination; Enrollment; Future; Generations; Genetic; Genomics; Goals; Heterogeneity; Individual; Kinetics; Lactate Dehydrogenase; Ligand Binding Domain; Malignant neoplasm of prostate; Measurement; Measures; Medical Genetics; Metastatic Prostate Cancer; Metastatic to; Modeling; Mutation; Neoplasm Circulating Cells; Outcome; Patient Care; Patients; Pattern; Phase; Phenotype; Physicians; Plasma; Predictive Value; Prevalence; Prior Therapy; Prognosis; RNA Splicing; Research Design; Resistance; Resistance development; Risk; Serum; Speed; Symptoms; Testing; Toxic effect; Treatment outcome; United States; Validation; Variant; abiraterone; androgen biosynthesis; angiokines; base; care delivery; castration resistant prostate cancer; chemotherapy; circulating biomarkers; clinical phenotype; design; disease heterogeneity; enzalutamide; genomic aberrations; genomic predictors; hormone therapy; improved; improved outcome; inhibitor; inhibitor therapy; insight; man; men; men' s group; novel; novel strategies; objective response rate; patient variability; phase III trial; predictive marker; predictive modeling; prognostic; prognostic model; prognostic value; radiological imaging; resistance mechanism; response; targeted treatment; taxane; therapy outcome; tumor; tumor DNA

ABSTRACT A major problem facing both physicians and men with metastatic prostate cancer is predicting whether a specific therapy will be effective. Currently, when a man develops metastatic castration resistant prostate cancer, the initial therapy is frequently an inhibitor of androgen receptor activity such as enzalutamide or abiraterone acetate. Following progression on hormonal therapies, taxane-based chemotherapy is frequently employed. While these therapies improve overall survival and delay progression, there is great heterogeneity between patients in the chances of clinical benefit, as defined by response rates and durations of responses. While most men develop resistance to these second generation hormonal therapies within 1-2 years, some men derive many years of benefit, while others do not respond or respond only transiently. Thus, an unmet need is the ability to identify those men most likely to have durable benefits from these therapies, while sparing those men unlikely to benefit the costs and toxicities associated with these agents. Predictive biomarkers provide such an opportunity to optimize care delivery in this setting and reduce the heterogeneity of this disease. In addition, such biomarkers will permit the design of novel approaches and clinical studies designed to improve outcomes in those men in greatest need.

抽象的 医师和男性转移性前列腺癌的一个主要问题正在预测 具体疗法将有效。目前，当一个人发展转移性cast割前列腺时 癌症，初始疗法通常是雄激素受体活性的抑制剂 乙酸阿比罗酮。在激素疗法进展后，基于紫杉烷的化学疗法经常是 雇用。尽管这些疗法改善了总体生存和延迟进展，但存在很大的异质性 在临床益处的机会中，患者之间的反应率和反应持续时间定义。 虽然大多数男性在1 - 2年内对这些第二代荷尔蒙疗法产生抵抗力，但有些 男性获得了多年的利益，而其他人则不暂时做出反应或反应。因此，一个未满足的 需求是能够识别最有可能从这些疗法中获得持久益处的男人，而在保留疗法的同时 这些男人不太可能受益于与这些药物相关的成本和毒性。预测生物标志物 提供了在此环境中优化护理交付的机会，并减少这种情况的异质性 疾病。此外，这样的生物标志物将允许设计新颖的方法和临床研究 在最需要的那些人中改善那些男人的结果。