Amplified therapeutic targets in high-grade serous ovarian carcinoma - a review of the literature with quantitative appraisal.
Amplified therapeutic targets in high-grade serous ovarian carcinoma - a review of the literature with quantitative appraisal.
复制标题
DOI：
10.1038/s41417-023-00589-z
复制
发表时间：
2023-07
影响因子：
6.4
通讯作者：
Aboagye EO
中科院分区：
文献类型：
--
作者：
Talbot T;Lu H;Aboagye EO
高级别浆液性卵巢癌是一种独特的癌症，其特征是普遍的TP 53突变和广泛的拷贝数改变。这些拷贝数改变包括肿瘤抑制基因的缺失和驱动癌基因的扩增。考虑到它们的关键致癌作用，扩增的驱动基因通常被提议作为治疗靶点。例如，抗HER 2药物的开发在临床上已成功治疗ERBB 2扩增的肿瘤。大范围的临床前工作已经研究了许多扩增的基因作为高级别浆液性卵巢癌的潜在治疗靶点。然而，可变的实验程序（例如，细胞系的选择）、模糊的表型或缺乏验证阻碍了许多靶的进一步临床转化。本文就高级别浆液性卵巢癌中可能作为扩增治疗靶点的基因进行综述，并对支持每个候选基因的证据进行定量评价。44个基因被发现有证据作为扩增的治疗靶点;得分最高的5个基因是CCNE 1、PAX 8、URI 1、PRKCI和RK 1。该评论生成了一份最新的扩增治疗靶点候选名单以供进一步开发，并提出了全面的标准来协助未来的扩增治疗靶点发现。
High-grade serous ovarian carcinoma is a unique cancer characterised by universal TP53 mutations and widespread copy number alterations. These copy number alterations include deletion of tumour suppressors and amplification of driver oncogenes. Given their key oncogenic roles, amplified driver genes are often proposed as therapeutic targets. For example, development of anti-HER2 agents has been clinically successful in treatment of ERBB2-amplified tumours. A wide scope of preclinical work has since investigated numerous amplified genes as potential therapeutic targets in high-grade serous ovarian carcinoma. However, variable experimental procedures (e.g., choice of cell lines), ambiguous phenotypes or lack of validation hinders further clinical translation of many targets. In this review, we collate the genes proposed to be amplified therapeutic targets in high-grade serous ovarian carcinoma, and quantitatively appraise the evidence in support of each candidate gene. Forty-four genes are found to have evidence as amplified therapeutic targets; the five highest scoring genes are CCNE1, PAX8, URI1, PRKCI and FAL1. This review generates an up-to-date list of amplified therapeutic target candidates for further development and proposes comprehensive criteria to assist amplified therapeutic target discovery in the future.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
3.7
作者：
Chen Y;McGee J;Chen X;Doman TN;Gong X;Zhang Y;Hamm N;Ma X;Higgs RE;Bhagwat SV;Buchanan S;Peng SB;Staschke KA;Yadav V;Yue Y;Kouros-Mehr H
通讯作者：
Kouros-Mehr H
DOI：
10.2147/dddt.s49584
发表时间：
2014
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Cekanova M;Rathore K
通讯作者：
Rathore K
影响因子：
64.8
作者：
通讯作者：
--