Targeting ARID1A-Deficient Cancers: An Immune-Metabolic Perspective

Epigenetic remodeling and metabolic reprogramming, two well-known cancer hallmarks, are highly intertwined. In addition to their abilities to confer cancer cell growth advantage, these alterations play a critical role in dynamically shaping the tumor microenvironment and antitumor immunity. Recent studies point toward the interplay between epigenetic regulation and metabolic rewiring as a potentially targetable Achilles' heel in cancer. In this review, we explore the key metabolic mechanisms that underpin the immunomodulatory role of AT-rich interaction domain 1A (ARID1A), the most frequently mutated epigenetic regulator across human cancers. We will summarize the recent advances in targeting ARID1A-deficient cancers by harnessing immune-metabolic vulnerability elicited by ARID1A deficiency to stimulate antitumor immune response, and ultimately, to improve patient outcome.

Automated summary

Epigenetic remodeling and metabolic reprogramming are two highly intertwined cancer hallmarks. Recent studies have shown that the interplay between epigenetic regulation and metabolic rewiring can be targeted as a potential Achilles' heel in cancer. This review explores the immunomodulatory role of ARID1A and summarizes the advances in targeting ARID1A-deficient cancers to improve patient outcome by harnessing the immune-metabolic vulnerability.