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

摘要 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 具体的治疗将是有效的。目前，当男性出现耐去势转移性前列腺癌时 对于癌症，最初的治疗通常是雄激素受体活性的抑制剂，如苯扎鲁胺或 醋酸阿比特龙。随着激素治疗的进展，以紫杉烷为基础的化疗经常 受雇的。虽然这些疗法提高了总体存活率并延缓了病情进展，但它们之间存在很大的异质性。 患者之间临床受益的机会，由应答率和应答持续时间定义。 虽然大多数男性在1-2年内对这些第二代激素疗法产生抵抗力，但也有一些人 男性获得多年的好处，而其他人不回应或只是暂时回应。因此，一个未被满足的人 需要的是能够识别哪些男性最有可能从这些疗法中获得持久的好处，而不是 这些男性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 提供这样的机会来优化这种环境中的护理交付，并减少 疾病。此外，这些生物标记物将允许设计新的方法和设计的临床研究 以改善那些最需要帮助的人的结果。

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.