Introduction: Poly(ADP-ribose) polymerase (PARP) inhibitors, including rucaparib, are the only targeted class of therapeutics approved for recurrent epithelial ovarian carcinoma with a predictive biomarker. Currently, three different PARP inhibitors are approved for either the treatment of ovarian cancer or maintenance of remission following chemotherapy. The Foundation Focus CDxBRCA is an FDA-cleared next-generation sequencing tumor tissue assay that detects somatic and sometimes germline mutations in BRCA1 and BRCA2 genes.Areas covered: The authors discuss the evolution of the ovarian cancer genomic testing landscape relative to PARP inhibition, with a focus on Foundation Focus CDxBRCA and CDxBRCA Loss of Heterozygosity (LOH), the complementary diagnostics (CDx) to rucaparib.Expert opinion: Relatively early in PARP inhibitor development, women with somatic and/or germline mutations in the BRCA1 and BRCA2 genes were found to have higher response rates to PARP inhibitors with longer durability than women who were BRCA wildtype. Other measures of homologous recombination deficiency including LOH have proven to be predictive biomarkers also. Because PARP biomarkers are genomic and complex, co-development of high-performance companion diagnostics was a high priority. The Foundation Focus test began as a next-generation sequencing assay capable of detecting germline (gBRCA) and somatic (sBRCA) mutations that predict response to rucaparib treatment. The addition of LOH to the assay was validated by a clinical trial supporting expansion of the Rucaparib FDA label to include maintenance of chemotherapy response.

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FoundationFocus CDxBRCA测试的配置文件。

简介：聚（ADP-核糖）聚合酶（PARP）抑制剂（包括rucaparib）是批准用于复发性上皮性卵巢癌且具有预测性生物标志物的唯一靶向治疗剂。目前，三种不同的PARP抑制剂被批准用于治疗卵巢癌或维持化疗后的缓解。Foundation Focus CDxBRCA是FDA批准的下一代测序肿瘤组织测定法，可检测BRCA1和BRCA2基因的体细胞突变，有时还检测种系突变。研究领域涉及：作者讨论了相对于PARP抑制作用的卵巢癌基因组检测格局的演变，以及专注于Foundation Focus CDxBRCA和CDxBRCA杂合子缺失（LOH），这是rucaparib的补充诊断剂（CDx）。专家意见：PARP抑制剂开发相对较早，发现具有BRCA1和BRCA2基因体细胞和/或种系突变的女性比野生型BRCA的女性对PARP抑制剂的反应率更高，并且具有更长的持久性。包括LOH在内的其他同源重组缺陷的措施也被证明是可预测的生物标志物。由于PARP生物标记物是基因组且复杂的，因此共同开发高性能伴随诊断程序是当务之急。Foundation Focus测试始于下一代测序测定法，该测定法能够检测出预测对rucaparib治疗反应的种系（gBRCA）和体细胞（sBRCA）突变。通过支持Rucaparib FDA标签扩展到包括维持化疗反应的临床试验验证了将LOH添加到该测定中。