ARID1A, also known as BAF250a, is a crucial subunit of the SWI/SNF chromatin remodeling complex. It binds DNA and plays a vital role in regulating gene expression that drives oncogenesis or tumor suppression. ARID1A participates in several key pathways such as the PI3K/AKT/mTOR pathway, immune responsiveness to cancer, EZH2 methyltransferase activity, steroid receptor modulation, DNA damage checkpoints, and regulation of p53 targets and KRAS signaling [2].

In murine models, ARID1A loss is sufficient to induce anti-tumor immune phenotypes seen in ARID1A mutant human cancers, including increased CD8+ T cell infiltration and cytolytic activity. ARID1A-deficient cancers upregulated an interferon (IFN) gene expression signature due to increased R-loops and cytosolic single-stranded DNA (ssDNA). This IFN signature and anti-tumor immunity were driven by STING-dependent type I IFN signaling, which was required for improved responsiveness of ARID1A mutant tumors to immune checkpoint blockade (ICB) treatment [1]. In addition, in a genetic clear cell ovarian carcinoma (OCCC) mouse model driven by conditional Arid1a inactivation, inhibitors of the mevalonate pathway such as simvastatin suppressed the growth of ARID1A mutant OCCCs and synergized with anti-PD-L1 antibody [3].

In conclusion, ARID1A is essential in regulating gene expression and participates in multiple critical pathways. Through KO/CKO mouse models, it has been revealed that ARID1A plays a significant role in anti-tumor immunity and the response to certain cancer treatments, especially in cancers like ovarian clear cell carcinomas and those responding to immune checkpoint blockade. These models have provided valuable insights into the functions of ARID1A in disease conditions, helping to understand the molecular mechanisms underlying cancer development and potentially guiding the development of more effective cancer therapies.