BARD1: A Friend or Foe in Pancreatic Ductal Adenocarcinoma?

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.

• Publication year

  2025

• Venue

  International Journal of Molecular Sciences

• Publication date

  2025-09-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/ijms26189041PMID 41009605PMCID 12470959
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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