Hein Kyaw Z, Stephen Bettzy, Fu Siqing
Department of Internal Medicine, HCA Florida Westside Hospital, Plantation, FL, USA.
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Immunother Precis Oncol. 2024 Feb 5;7(1):41-52. doi: 10.36401/JIPO-22-37. eCollection 2024 Feb.
AT-rich interaction domain 1A (ARID1A), a mammalian switch/sucrose nonfermenting complex subunit, modulates several cellular processes by regulating chromatin accessibility. It is encoded by , an immunosuppressive gene frequently disrupted in a many tumors, affecting the proliferation, migration, and invasion of cancer cells. Targeting molecular pathways and epigenetic regulation associated with ARID1A loss, such as inhibiting the PI3K/AKT pathway or modulating Wnt/β-catenin signaling, may help suppress tumor growth and progression. Developing epigenetic drugs like histone deacetylase or DNA methyltransferase inhibitors could restore normal chromatin structure and function in cells with ARID1A loss. As deficiency correlates with enhanced tumor mutability, microsatellite instability, high tumor mutation burden, increased programmed death-ligand 1 expression, and T-lymphocyte infiltration, ARID1A-deficient cells can be a potential therapeutic target for immune checkpoint inhibitors that warrants further exploration. In this review, we discuss the role of in carcinogenesis, its crosstalk with other signaling pathways, and strategies to make ARID1A-deficient cells a potential therapeutic target for patients with cancer.
富含AT的相互作用结构域1A（ARID1A）是一种哺乳动物的SWI/SNF复合物亚基，通过调节染色质可及性来调控多种细胞过程。它由 编码，是一种在许多肿瘤中经常被破坏的免疫抑制基因，影响癌细胞的增殖、迁移和侵袭。靶向与ARID1A缺失相关的分子途径和表观遗传调控，如抑制PI3K/AKT途径或调节Wnt/β-连环蛋白信号传导，可能有助于抑制肿瘤生长和进展。开发组蛋白去乙酰化酶或DNA甲基转移酶抑制剂等表观遗传药物可以恢复ARID1A缺失细胞中的正常染色质结构和功能。由于 缺陷与肿瘤突变性增强、微卫星不稳定性、高肿瘤突变负担、程序性死亡配体1表达增加和T淋巴细胞浸润相关，ARID1A缺陷细胞可能是免疫检查点抑制剂的潜在治疗靶点，值得进一步探索。在这篇综述中，我们讨论了 在致癌作用中的作用、它与其他信号通路的相互作用，以及使ARID1A缺陷细胞成为癌症患者潜在治疗靶点的策略。 （注：原文中存在部分未明确的表述，已按原样翻译）
