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BARD1: A Friend or Foe in Pancreatic Ductal Adenocarcinoma?
Lily Zekavat1, Aditi Jain1,2
1Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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.
Insights
BARD1 (BRCA1-Associated RING Domain 1) has dual roles in pancreatic cancer, acting as a tumor suppressor or driver. Understanding its context-dependent functions is key for developing new DNA damage response (DDR) therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes.
- DNA repair pathways, especially homologous recombination (HR), are critical in cancer development and treatment.
- BARD1 (BRCA1-Associated RING Domain 1) has a complex, context-dependent role in tumor biology.
Purpose of the Study:
- To review the dual roles of BARD1 and its isoforms in PDAC.
- To examine BARD1 regulation and its impact on DNA repair, apoptosis, and drug resistance.
- To evaluate the therapeutic potential of targeting BARD1 and DNA damage response (DDR) pathways in PDAC.
Main Methods:
- Literature review of BARD1's function in PDAC.
- Analysis of evidence on BARD1 isoform effects on DNA repair and drug resistance.
- Summary of ongoing clinical trials targeting DDR in PDAC.
Main Results:
- BARD1 exhibits context-dependent tumor suppressor or oncogenic driver activities in PDAC.
- BARD1 isoforms differentially influence DNA repair, apoptosis, and drug resistance.
- Targeting BARD1 and DDR pathways shows therapeutic potential for PDAC.
Conclusions:
- BARD1's role in PDAC is complex and depends on its isoforms and cellular environment.
- Profiling BARD1 isoforms is essential for understanding its functions in PDAC.
- Exploiting DDR vulnerabilities through precision oncology offers promising therapeutic strategies for PDAC.
