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上皮性卵巢癌中药物治疗敏感性预测性蛋白质基因组生物标志物的机遇。

Opportunities for predictive proteogenomic biomarkers of drug treatment sensitivity in epithelial ovarian cancer.

作者信息

Philips Trudy J, Erickson Britt K, Thomas Stefani N

机构信息

Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota School of Medicine, Minneapolis, MN, United States.

Department of Obstetrics, Gynecology and Women's Health, University of Minnesota School of Medicine, Minneapolis, MN, United States.

出版信息

Front Oncol. 2025 Jan 7;14:1503107. doi: 10.3389/fonc.2024.1503107. eCollection 2024.

Abstract

Genomic analysis has played a significant role in the identification of driver mutations that are linked to disease progression and response to drug treatment in ovarian cancer. A prominent example is the stratification of epithelial ovarian cancer (EOC) patients with homologous recombination deficiency (HRD) characterized by mutations in DNA damage repair genes such as for treatment with PARP inhibitors. However, recent studies have shown that some epithelial ovarian tumors respond to PARP inhibitors irrespective of their HRD or mutation status. An exclusive focus on the genome overlooks the significant insight that can be gained from other biological analytes, including proteins, which carry out cellular functions. Proteogenomics is the integration of genomics, transcriptomics, epigenomics and proteomics data. This review paper provides novel insight into the role of proteogenomics as an analytical approach to identify predictive biomarkers of drug treatment response in epithelial ovarian cancer. Proteogenomic analysis can facilitate the identification of predictive biomarkers of drug treatment response, consequently greatly improving the stratification of patients with EOC for treatment towards a goal of personalized medicine.

摘要

基因组分析在识别与卵巢癌疾病进展和药物治疗反应相关的驱动突变方面发挥了重要作用。一个突出的例子是对同源重组缺陷(HRD)的上皮性卵巢癌(EOC)患者进行分层,这些患者的特征是DNA损伤修复基因发生突变,例如用于接受PARP抑制剂治疗。然而,最近的研究表明,一些上皮性卵巢肿瘤无论其HRD或突变状态如何,都对PARP抑制剂有反应。仅关注基因组忽略了从其他生物分析物(包括执行细胞功能的蛋白质)中可以获得的重要见解。蛋白质基因组学是基因组学、转录组学、表观基因组学和蛋白质组学数据的整合。这篇综述文章为蛋白质基因组学作为一种分析方法在识别上皮性卵巢癌药物治疗反应预测生物标志物方面的作用提供了新的见解。蛋白质基因组学分析可以促进药物治疗反应预测生物标志物的识别,从而极大地改善EOC患者的分层治疗,朝着个性化医疗的目标迈进。

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Homologous recombination deficiency and ovarian cancer.同源重组缺陷与卵巢癌
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