ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer

Nan, Lingxi; Wang, Changcheng; Wang, Jie; Zhang, Shulong; Bo, Xiaobo; Wang, Yueqi; Liu, Houbao

doi:10.3389/fonc.2022.787897

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…CD274 , which encodes PD-L1, is transcriptionally repressed by ARID1A [ 57 ]. As a result, loss of ARID1A predicts increased PD-L1 expression [ 58 ] via activating AKT signaling [ 59 , 60 ]. These data suggest that ARID1A loss may help cancer cells, especially those with MMR deficiency, escape from immune checkpoint surveillance through upregulation of PD-L1.…”

Section: Arid1a Dna Mismatch Repair and Immune Checkpointmentioning

confidence: 99%

Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response

Mandal

Wang

et al. 2022

J Biomed Sci

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Chromatin remodeling is an essential cellular process for organizing chromatin structure into either open or close configuration at specific chromatin locations by orchestrating and modifying histone complexes. This task is responsible for fundamental cell physiology including transcription, DNA replication, methylation, and damage repair. Aberrations in this activity have emerged as epigenomic mechanisms in cancer development that increase tumor clonal fitness and adaptability amidst various selection pressures. Inactivating mutations in AT-rich interaction domain 1A (ARID1A), a gene encoding a large nuclear protein member belonging to the SWI/SNF chromatin remodeling complex, result in its loss of expression. ARID1A is the most commonly mutated chromatin remodeler gene, exhibiting the highest mutation frequency in endometrium-related uterine and ovarian carcinomas. As a tumor suppressor gene, ARID1A is essential for regulating cell cycle, facilitating DNA damage repair, and controlling expression of genes that are essential for maintaining cellular differentiation and homeostasis in non-transformed cells. Thus, ARID1A deficiency due to somatic mutations propels tumor progression and dissemination. The recent success of PARP inhibitors in treating homologous recombination DNA repair-deficient tumors has engendered keen interest in developing synthetic lethality-based therapeutic strategies for ARID1A-mutated neoplasms. In this review, we summarize recent advances in understanding the biology of ARID1A in cancer development, with special emphasis on its roles in DNA damage repair. We also discuss strategies to harness synthetic lethal mechanisms for future therapeutics against ARID1A-mutated cancers.

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Section: Arid1a Dna Mismatch Repair and Immune Checkpointmentioning

confidence: 99%

Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response

Mandal

Wang

et al. 2022

J Biomed Sci

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“…The ARID1A deficiency interferes with the immune checkpoint and predicts microsatellite instability and overexpression of PD-L1 [ 83 ]. Consequently, PD-L1 inhibitors might have a promising role in ARID1A -mutant ICC.…”

Section: Resultsmentioning

confidence: 99%

Molecular Profile of Intrahepatic Cholangiocarcinoma

Andraus,

Tustumi,

de Meira Junior

et al. 2023

IJMS

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Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease’s underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC’s molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.

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ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer

Cited by 2 publications

References 39 publications

Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response

Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response

Molecular Profile of Intrahepatic Cholangiocarcinoma

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