高级别浆液性卵巢癌（HGSOC）是最致命的卵巢癌，独占其所有亚型的90％。HGSOC具有TP53的标志性突变，显示出多样的分子病因学。HGSOC既可以起源于卵巢上皮，也可以起源于输卵管的囊状上皮。排卵引起的反应性氧化应激，卵泡液相关的生长因子引起的干细胞特性，ER、FSHR、AR等激素受体的失调，FSH、LH等激素，长时间的排卵周期，口服避孕药的使用是HGSOC的激动剂，而生育和哺乳提供了对HGSOC发展的保护作用。除了通用的TP53突变外，据报道BRCA1/2、RAD51、BRIP1、PALB2、CHEK2、RAD50等基因的突变与HGSOC的发展相关。还报道了HGSOC中RAS信号通路的RASSF1A、OR51L1、OR51I1、OR51F1等的甲基化等表观遗传事件。据报道，miR-1290、miR-27-a-3p、miR23a、miR205等微小RNA在HGSOC中上调。在不同的亚型中，分化型、免疫反应型、间质型和增殖型HGSOC显示了最差的预后。系统生物学方法显示HGSOC中的五条主要改变的信号通路，分别为RB、PI3K/RAS、NOTCH、HRR和FOXM1信号通路。对于化疗前的患者，能够促进还原型谷胱甘肽的外流或阻止GSH-GSSG的氧化还原偶联的药物，如顺铂，可能是治疗HGSOC的最佳选择。对于具有BRCA1/2突变的患者，单独或与贝伐单抗联用的PARP抑制剂可能有效。免疫检查点抑制剂可能对免疫反应型HGSOC有效。识别在化疗耐药中发生失调的基因可能提供更好的治疗洞察。© 2023. The Author(s), under exclusive licence to Springer Nature B.V.

High-grade serous ovarian carcinoma (HGSOC), the deadliest ovarian cancer, alone accounts for 90% of all its subtypes. Characterized by hallmark mutation of TP53, HGSOC show diverse molecular etiology. HGSOC can arise from both ovarian epithelium as well as the fimbrial epithelium of the fallopian tube. Ovulation induced reactive oxygen species, follicular fluid associated growth factor induced stemness, deregulation of hormone receptors like ER, FSHR, AR and hormones like FSH, LH, prolonged ovulation cycle, use of oral contraceptives are agonists of HGSOC while parity, breastfeeding provide protective effect from HGSOC development. Apart from a generic TP53 mutation, mutation of BRCA1/2, RAD51, BRIP1, PALB2, CHEK2, RAD50 etc., were reportedly associated with development of HGSOC. Epigenetic events like methylation of RASSF1A of RAS signaling pathway,OR51L1, OR51I1, OR51F1 etc. has been reported in HGSOC. Micro-RNAs like miR-1290, miR 27-a-3p miR23a, miR205 were reportedly upregulated in HGSOC. Amongst its cognate subtypes viz. differentiated, immunoreactive, mesenchymal, and proliferative, mesenchymal, and proliferative show worst prognosis. A system biology approach showed five major altered pathways in HGSOC, namely, RB, PI3K/RAS, NOTCH, HRR and FOXM1 signaling. For chemonaive patients, drugs that helps in efflux of reduced glutathione or prevent the redox coupling of GSH-GSSG, like Cisplatin, could be considered as the best therapeutic choice for HGSOC. For patients with BRCA1/2 mutations, PARP inhibitors alone or with Bevacizumab can be effective. Immune checkpoint inhibitors could be effective against immunoreactive subtypes. Identification of genes deregulated in chemoresistance could provide better insights in dealing with the disease.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.