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: 10620612
• 负责人: Andrew J Armstrong
• 金额: $ 63.69万
• 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/10620612
• 关键词: AR gene; Acceleration; Acetates; Alkaline Phosphatase; Androgen Antagonists; Androgen Receptor; Androgens; Biological Markers; Biology; Cancer Etiology; 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; Modeling; Mutation; Neoplasm Circulating Cells; Outcome; Patients; Pattern; Phase; Phenotype; Physicians; Plasma; Prediction of Response to Therapy; 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; care delivery; castration resistant prostate cancer; chemotherapy; circulating biomarkers; clinical phenotype; design; direct patient care; 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 医生和患有转移性前列腺癌的男性面临的一个主要问题是预测是否会发生转移性前列腺癌。 具体治疗才会有效果。目前，当一名男性出现转移性去势抵抗性前列腺时 癌症时，初始治疗通常是雄激素受体活性抑制剂，例如恩杂鲁胺或 醋酸阿比特龙。随着激素疗法的进展，基于紫杉烷的化疗经常被采用 受雇。虽然这些疗法可以提高总体生存率并延缓进展，但存在很大的异质性 患者之间临床获益的机会，由反应率和反应持续时间定义。 虽然大多数男性会在 1-2 年内对这些第二代激素疗法产生耐药性，但有些男性 男性受益多年，而其他人则没有反应或仅短暂反应。于是，一个未满足的 需要的是能够识别那些最有可能从这些疗法中获得持久益处的男性，同时避免 这些人不太可能从与这些药物相关的成本和毒性中受益。预测性生物标志物 提供这样一个机会来优化这种情况下的护理服务并减少这种情况的异质性 疾病。此外，此类生物标志物将允许设计新方法和临床研究 改善最需要帮助的男性的治疗结果。