Sisman Yagmur, Vestergaard Lau Kræsing, de Oliveira Douglas Nogueira Perez, Poulsen Tim Svenstrup, Schnack Tine Henrichsen, Høgdall Claus, Høgdall Estrid
Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
Department of Gynecology, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Pharmaceuticals (Basel). 2022 Oct 26;15(11):1324. doi: 10.3390/ph15111324.
We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC).
We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS.
47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib.
PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings.
我们旨在使用下一代测序（NGS）鉴定体细胞致病和可能致病的突变。将突变结果与临床详细描述的数据进行对照，以确定丹麦高级别浆液性卵巢癌（HGSC）患者的潜在靶向治疗方法。
我们对128例HGSC患者的突变谱进行了特征分析。临床数据来自丹麦妇科数据库，组织样本通过丹麦癌症生物库收集。使用NGS分析DNA。
47例（37%）患者对铂敏感，32例（25%）部分对铂敏感，35例（27%）对铂耐药，3例（2%）对铂难治，11例（9%）患者未接受化疗。总体而言，27例（21%）有已知的可靶向治疗靶点。12例（26%）铂敏感患者有PARP抑制剂的可靶向治疗靶点：1例有酪氨酸激酶抑制剂靶点，1例有免疫治疗靶点。8例（25%）部分铂敏感患者有可靶向治疗靶点：7例符合PARP抑制剂治疗条件，1例可能符合阿培利司和激素治疗条件。7例（20%）铂耐药患者有可靶向治疗靶点：6例（86%）可能符合PARP抑制剂治疗条件，1例有免疫治疗靶点，1例有厄达替尼靶点。
PARP抑制剂是HGSC中最常见的潜在靶向治疗方法。然而，根据我们的突变结果，其他靶向治疗方法仍值得研究。
