Murali Roopak, Balasubramaniam Vaishnavi, Srinivas Satish, Sundaram Sandhya, Venkatraman Ganesh, Warrier Sudha, Dharmarajan Arun, Gandhirajan Rajesh Kumar
Department of Human Genetics, Faculty of Biomedical Sciences Technology and Research, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Porur, Chennai 600116, India.
Department of Radiation Oncology, Sri Ramachandra Medical College & Research Institute, Sri Ramachandra Institute of Higher Education & Research (Deemed to be University), Porur, Chennai 600116, India.
Metabolites. 2023 Apr 15;13(4):560. doi: 10.3390/metabo13040560.
Ovarian cancers are tumors that originate from the different cells of the ovary and account for almost 4% of all the cancers in women globally. More than 30 types of tumors have been identified based on the cellular origins. Epithelial ovarian cancer (EOC) is the most common and lethal type of ovarian cancer which can be further divided into high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. Ovarian carcinogenesis has been long attributed to endometriosis which is a chronic inflammation of the reproductive tract leading to progressive accumulation of mutations. Due to the advent of multi-omics datasets, the consequences of somatic mutations and their role in altered tumor metabolism has been well elucidated. Several oncogenes and tumor suppressor genes have been implicated in the progression of ovarian cancer. In this review, we highlight the genetic alterations undergone by the key oncogenes and tumor suppressor genes responsible for the development of ovarian cancer. We also summarize the role of these oncogenes and tumor suppressor genes and their association with a deregulated network of fatty acid, glycolysis, tricarboxylic acid and amino acid metabolism in ovarian cancers. Identification of genomic and metabolic circuits will be useful in clinical stratification of patients with complex etiologies and in identifying drug targets for personalized therapies against cancer.
卵巢癌是起源于卵巢不同细胞的肿瘤，占全球女性所有癌症的近4%。基于细胞起源已鉴定出30多种肿瘤类型。上皮性卵巢癌（EOC）是最常见且致命的卵巢癌类型，可进一步分为高级别浆液性癌、低级别浆液性癌、子宫内膜样癌、透明细胞癌和黏液性癌。卵巢癌发生长期以来被归因于子宫内膜异位症，这是一种生殖道慢性炎症，导致突变逐渐积累。由于多组学数据集的出现，体细胞突变的后果及其在改变肿瘤代谢中的作用已得到充分阐明。几种癌基因和肿瘤抑制基因与卵巢癌的进展有关。在本综述中，我们重点介绍了导致卵巢癌发生的关键癌基因和肿瘤抑制基因所经历的遗传改变。我们还总结了这些癌基因和肿瘤抑制基因的作用，以及它们与卵巢癌中脂肪酸、糖酵解、三羧酸和氨基酸代谢失调网络的关联。鉴定基因组和代谢回路将有助于对病因复杂的患者进行临床分层，并确定针对癌症个性化治疗的药物靶点。
