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.

摘要 医生和转移性前列腺癌患者面临的一个主要问题是， 具体的治疗是有效的。目前，当一个人发展成转移性去势抵抗性前列腺时， 对于癌症，初始治疗通常是雄激素受体活性的抑制剂，如恩杂鲁胺或 醋酸阿比特龙激素治疗进展后，紫杉烷为基础的化疗往往是 就业。虽然这些疗法改善了总体生存率并延迟了进展，但存在很大的异质性。 根据缓解率和缓解持续时间的定义，患者之间的临床获益机会。 虽然大多数男性在1-2年内对这些第二代激素疗法产生耐药性，但一些男性在1-2年内对这些第二代激素疗法产生耐药性。 男子可获得多年的好处，而其他人则不作出反应或只是暂时作出反应。因此， 需要的是能够确定那些最有可能从这些疗法中获得持久益处的男性，同时保留 这些人不太可能受益于与这些药物相关的成本和毒性。预测性生物标志物 提供这样一个机会，以优化在这种情况下的护理提供，并减少这种异质性， 疾病此外，这些生物标志物将允许设计新的方法和临床研究， 来改善那些最需要帮助的人的治疗效果。