Conceptual frameworks of synthetic lethality in clear cell carcinoma of the ovary (Review)

Abstract

Abstract. Targeting non-oncogenes may result in the selective death of cancer cells. Clear cell carcinoma of the ovary (CCC) may exhibit resistance against conventional chemotherapy and is associated with poor prognosis. The aim of the present report was to review synthetic lethality-based therapies for CCC. Previous English-language studies were reviewed to accumulate preclinical and clinical data on targeting synthetic lethal partners. Synthetic lethal interactions have a variety of types, involving components of a backup or parallel pathway with overlapping functions, components encoded by paralogous pairs, subunit components that form heteromeric complexes and components that are arranged in a single linear pathway. A set of candidate gene targets potentially resulting in synthetic lethality have been previously identified. HNF class homeobox, AT-rich interaction domain 1A, ATR serine/threonine kinase, ATM serine/threonine kinase, checkpoint kinase 1 and phosphatase and tensin homolog may be the key partner genes. A variety of loss of function genes in CCC are driver or passenger events and may function as synthetic lethal pairs under replication stress conditions. Further clinical studies will be required to investigate the safety and therapeutic effect of synthetic lethality pairs in CCC tumor types with replication stress.

BRM: the core ATPase subunit of SWI/SNF chromatin-remodelling complex—a tumour suppressor or tumour-promoting factor?

“…Many of them control cellular processes such as metabolism (including drug metabolism), DNA repair, differentiation, adhesion and apoptosis, and are involved in angiogenesis, progression or metastasis of cancer [31]. Recent studies on ovarian cancer revealed that BRG1 and BRM ATPases are mutually exclusive as their parallel inactivation leads to synthetic lethality [32], although other reports indicated the survival of cells with depletion of both ATPases [31]. One possible explanation of this apparent discrepancy may be the existence of shorter, truncated but functional versions of BRM protein which are simply not recognised by the anti-BRM antibody.…”

CDK1 as a Novel Potential Biomarker for Predicting the Prognosis of endometrioid ovarian carcinoma

“…In this study, CDK1 was selected as a hub gene through bioinformatic analysis. To evaluate the potential of CDK1 as a prognostic biomarker for EOC, the expression of CDK1 was compared between EOC tissues and endometriosis lesions, which are considered to be precursors to EOC 20,21 . The relationship between CDK1 expression and clinicopathological features or prognosis data was assessed to determine the value of CDK1 in predicting the prognosis of EOC patients.…”