Wise Management of Ovarian Cancer: On the Cutting Edge.
Stergios BoussiosChristos MikropoulosEleftherios SamartzisPeeter KarihtalaMichele MoschettaMatin SheriffAfroditi KarathanasiAgne SadauskaiteElie RassyNicholas PavlidisPublished in: Journal of personalized medicine (2020)
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20-40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations.
Keyphrases
- copy number
- dna repair
- genome wide
- genome wide identification
- dna damage
- end stage renal disease
- genome wide analysis
- protein kinase
- germ cell
- chronic kidney disease
- single molecule
- ejection fraction
- newly diagnosed
- dna methylation
- transcription factor
- cardiovascular events
- breast cancer risk
- polycystic ovary syndrome
- single cell
- papillary thyroid
- peritoneal dialysis
- squamous cell carcinoma
- artificial intelligence
- electronic health record
- skeletal muscle
- big data
- gene expression
- cell therapy
- endometrial cancer
- coronary artery disease
- oxidative stress
- metabolic syndrome
- risk factors
- childhood cancer
- patient reported outcomes
- bioinformatics analysis
- smoking cessation
- bone marrow
- free survival
- structural basis
- cardiovascular disease