Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Sep 15;14(9):5952-5964.
eCollection 2022.

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

Ruichao Li  1 , Guangbing Xiong  2 , Jun Zhao  3 , Lin Yang  4
Affiliations
Review

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

Ruichao Li et al. Am J Transl Res. .

Abstract

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.

Keywords: AT-rich interactive domain 1A (ARID1A); biomarker; pancreatic cancer; prognosis; tumorigenesis.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
The inactive alterations of ARID1A attribute to the carcinogenesis of PDAC. PanINs, pancreatic intraepithelial neoplasias; IPMNs, intraductal papillary mucinous neoplasms; PDAC, pancreatic ductal adenocarcinoma; EMT, epithelial-mesenchymal transition.
Figure 2
Figure 2
Mechanisms of ARID1A alterations contributing to sensitivity of pancreatic cancer to targeted agents, ICB immunotherapy, and the combinations. HR, homologous recombination; DDR, DNA damage Repair; MSI-H, microsatellite instability-high; PARP, poly ADP-ribose polymerase; ICB, immune checkpoint blockade; TMB, tumor mutation burden; TME, tumor microenvironment; ICIs, immune checkpoint inhibitors.
See this image and copyright information in PMC

References

    1. Zheng RS, Sun KX, Zhang SW, Zeng HM, Zou XN, Chen R, Gu XY, Wei WW, He J. Report of cancer epidemiology in China, 2015. Zhonghua Zhong Liu Za Zhi. 2019;41:19–28. - PubMed
    1. Lin QJ, Yang F, Jin C, Fu DL. Current status and progress of pancreatic cancer in China. World J Gastroenterol. 2015;21:7988–8003. - PMC - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. - PubMed
    1. Wood LD, Canto MI, Jaffee EM, Simeone DM. Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment. Gastroenterology. 2022;163:386–402. e1. - PMC - PubMed
    1. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 2007;25:1960–1966. - PubMed

LinkOut - more resources