Document Type

Article

Publication Date

9-17-2025

Comments

This article is the author’s final published version in International Journal of Molecular Sciences, Volume 26, Issue 18, 2025, Article number 9041.

The published version is available at https://doi.org/10.3390/ijms26189041. Copyright © 2025 by the authors.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with poor overall prognosis and limited response to standard treatments. Growing interest in the modulation of DNA repair mechanisms, including the homologous recombination (HR) repair pathway, has opened new avenues for therapeutic development. BARD1 (BRCA1-Associated RING Domain 1) plays a complex role in tumor biology, functioning either as a tumor suppressor or as an oncogenic driver, depending on isoform expression, cellular context, and regulatory environment. In this review, we examine the dual roles of BARD1, focusing on its regulation and paradoxical activities in PDAC. We summarize evidence that BARD1 and BARD1 isoforms differentially affect DNA repair, apoptosis, and drug resistance and evaluate the therapeutic potential of targeting BARD1 and other DNA damage response (DDR) proteins. We also review ongoing clinical trials and investigational agents designed to exploit DDR vulnerabilities in PDAC. Together, these insights highlight BARD1's context-dependent roles in PDAC and support continued efforts to profile BARD1 isoforms, clarify their functions, and leverage DDR pathways through precision oncology approaches.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

41009605

Language

English

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