The Role of CtIP in Breast Cancer Development and Treatment - an overview

Breast cancer accounts for the highest incidence and mortality rate of all female cancers. Early detection is important for the effectiveness of treatment and thereby survival rate. In respect to detection, unraveling of genes and proteins involved in development of breast cancer is essential. Knowledge about genes that predispose women to breast cancer can provide application of preventive measures. Moreover, identification of factors that contribute to tumorigenesis would provide targets for treatment of this severe disease. CtIP is a possible candidate to be a contributing factor in development of breast cancer. This protein has been shown to be involved in transcriptional regulation, cell cycle regulation, and DNA damage repair, all of which can be disturbed in case of cancer. Genomic screening of CtIP in tumor cell lines did not show somatic mutations and screening of breast cancer cell lines did not identify any germline variants. There is not enough known about differences in CtIP mRNA/protein expression between cancer cells and normal cells. Other ways by which CtIP function can be altered, possibly leading to tumor genesis, are post-translational modification and protein-protein interactions. CtIP needs several post-translational steps to exert its functions, like phosphorylation, deacetylation, and ubiquitination. Inhibition of those steps might result in depleted CtIP function. CtIP also interacts with a lot of proteins, and loss of those interactions could have the same result. Research is needed to confirm those theories. The role of CtIP in DNA repair by homologous recombination might have therapeutic implications. BRCA1 and BRCA2 (genes involved in predisposition to breast cancer) act in the same DNA repair pathway. Therapy based on synthetic lethality by inhibition of PARP has been shown to be a promising therapeutic agent in BRCA1 or BRCA2 mutated cancers. The same therapy might be applicable in case of cancers with (induced) altered CtIP function. However, future research is needed to demonstrate involvement of CtIP in breast cancer development and the potential therapeutic implications that might have.