Targeting the alterations of ARID1A in pancreatic cancer: tumorigenesis, prediction of treatment, and prognostic value.

The chromatin remodeling gene AT-rich interactive domain 1A (ARID1A), encoding a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is one of the most frequently mutated chromatin regulators across a broad spectrum of cancers. Most of the ARID1A alterations are inactivating, leading to the loss or reduced expression of the protein. Recently, ARID1A has been demonstrated as a tumor suppressor gene in pancreatic ductal adenocarcinoma (PDAC), as its inactive alterations attribute to carcinogenesis. Importantly, ARID1A alterations are revealed as predictive biomarkers for the selection of targeted therapy and immune checkpoint blockade (ICB) therapy. In PDAC, the application of ARID1A alterations in stratifying patients for precise treatment has also been widely explored in preclinical and early clinic studies with encouraging preliminary results. Furthermore, the prognostic value of ARID1A mutations in PDAC has been suggested by various studies. In this review, we focus on the functions of ARID1A alterations in PDAC, particularly their functions during carcinogenesis and their predictive value in treatment selection and prognosis, to provide a comprehensive overview on our current understanding of ARID1A alterations in PDAC. AJTR