Targeting ARID1A-Deficient Cancers: An Immune-Metabolic Perspective

Cells. 2023 Mar 21;12(6):952. doi: 10.3390/cells12060952.

Abstract

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.

Keywords: ARID1A; cancer immunotherapy; chromatin remodeling; metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic
  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Nuclear Proteins / metabolism
  • Transcription Factors* / metabolism
  • Tumor Microenvironment

Substances

  • ARID1A protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors

Grants and funding

This research was funded by the Andrew McDonough B+ (Be Positive) Foundation’s Childhood Cancer Research Award, the Children’s Cancer Research Fund’s Emerging Scientist Award, the National Science and Technology Council (MOST 110-2311-B-039-001 and MOST 111-2320-B-039-050), and China Medical University (CMU109-YT-03). X.-G.L. was an Infinite Love for Kids Fighting Cancer Independent Investigator and Bear Necessities Pediatric Cancer Foundation Independent Investigator (No: 19IN31).