The role of ARID1A in malignant neoplasms of the female reproductive system: a modern view on the possibilities of diagnosis and therapy

Abstract

Сhromatin remodeling tumor suppressor protein ARID1A (AT-rich interaction domain 1A) is coded by the ARID1A gene that is one of the most frequently mutated genes of human oncological diseases. Inactivating mutations in the ARID1A gene have a pronounced effect on cell survival, chemoresistance, transcription and regulation of the cell cycle. To date, a large number of studies have focused on assessing the effect of mutations leading to loss of ARID1A function on the occurrence, progression and resistance of tumors to therapy. The high frequency of ARID1A mutations in malignant tumors of the female reproductive system opens up unique opportunities for targeted preventive and therapeutic intervention. Clear cell carcinoma of the ovaries and uterine body cancer with ARID1A mutations do not respond well to standard chemotherapy and, to date, do not have effective targeted therapy, which underlines the need for further research in this area. ARID1A can be used as a biomarker of precancerous diseases, as well as as a tool for predicting the response to radiation therapy, immunotherapy and targeted therapies. Currently, clinical trials of several low molecular weight and epigenetic inhibitors are being conducted in tumors of the female reproductive system with ARID1A deficiency.