Abstract：
PARP inhibitors, such as rucaparib, have been well characterized in metastatic castration-resistant prostate cancer (mCRPC) associated with BRCA alterations, and the clinical activity of these agents has also been evaluated in patients with mCRPC associated with alterations in other non-BRCA DNA damage repair (DDR) genes, including RAD51B. There is likely a differential sensitivity to PARP inhibition based on the specific DDR gene altered, but research in this area is limited because of the low frequency of alterations in these genes. Here, we describe a mCRPC patient with a truncating rearrangement of RAD51B who had a radiographic and PSA response when treated with the PARP inhibitor rucaparib within the TRITON2 trial. We investigated the patients\' response parameters, circulating tumor DNA (ctDNA) fraction and tumor genomics longitudinally, using next-generation sequencing (NGS) of tissue and plasma. ctDNA fraction correlates with radiographic and PSA response and is lower during times of response. NGS did not reveal any potential genomic mechanism of acquired drug resistance. This case shows evidence for rucaparib activity in a rare patient with mCRPC and a RAD51B truncation.
摘要：
PARP抑制剂,比如rucaparib,在与BRCA改变相关的转移性去势抗性前列腺癌（mCRPC）中已得到很好的表征，这些药物的临床活性也在mCRPC患者中进行了评估，这些患者与其他非BRCADNA损伤修复（DDR）基因的改变有关，包括RAD51B。基于特定的DDR基因改变，可能对PARP抑制有不同的敏感性，但是由于这些基因的改变频率低，这方面的研究是有限的。这里,我们描述了1例RAD51B截短重排的mCRPC患者在TRITON2试验中接受PARP抑制剂rucaparib治疗时出现影像学和PSA应答.我们调查了患者的反应参数，循环肿瘤DNA（ctDNA）部分和肿瘤基因组学纵向，使用组织和血浆的下一代测序（NGS）。ctDNA分数与放射学和PSA反应相关,并且在反应期间较低。NGS没有揭示获得性耐药的任何潜在基因组机制。此病例显示了罕见的mCRPC和RAD51B截短患者中鲁卡帕尼活性的证据。
