Targeting BARD1 suppresses a Myc-dependent transcriptional program and tumor growth in pancreatic ductal

Related Experiment Video

Updated: May 21, 2025

Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue
10:11

Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue

Published on: January 3, 2013

23.0K

Sohum Patel1, Eleanor Jenkins1, Rutuj P Kusurkar1

  • 1Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Neoplasia (New York, N.Y.)
|March 17, 2025
PubMed

Insights

BARD1 protein is overexpressed in pancreatic cancer, driving tumor growth by stabilizing c-Myc. Inhibiting BARD1 effectively blocks PDAC growth and enhances cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options.
  • The role of BARD1 (BRCA1-Associated Ring Domain-1) in PDAC pathogenesis and its molecular mechanisms are not fully understood.
  • BARD1 is crucial for homologous recombination repair (HRR), a pathway often dysregulated in cancer.

Purpose of the Study:

  • To investigate the function and therapeutic potential of BARD1 in pancreatic ductal adenocarcinoma.
  • To elucidate the molecular mechanisms by which BARD1 influences PDAC progression.
  • To evaluate the efficacy of targeting BARD1 in combination with existing therapies.

Main Methods:

  • Assessed BARD1 expression levels in PDAC tissues.
  • Utilized siRNA and CRISPR/Cas9 to inhibit BARD1 genetically.
  • Investigated the effect of BARD1 inhibition on c-Myc expression and downstream targets.
  • Examined the impact of BARD1 targeting on PDAC cell growth in vitro and in vivo.
  • Screened a drug library of DNA damage response compounds for synergistic effects with BARD1 inhibition.

Main Results:

  • BARD1 is significantly overexpressed in PDAC.
  • Genetic inhibition of BARD1 suppressed c-Myc and its transcriptional program.
  • BARD1 was found to stabilize c-Myc via the ubiquitin-proteasome system by regulating FBXW7.
  • Targeting BARD1 inhibited PDAC growth in vitro and in vivo with no observed toxicity in mice.
  • BARD1 inhibition potentiated the efficacy of DNA damage response agents, including PARPi, in HRR-proficient PDAC cells.

Conclusions:

  • BARD1 plays a critical role in PDAC progression by stabilizing c-Myc.
  • Targeting BARD1 represents a promising therapeutic strategy for HRR-proficient PDAC.
  • Combined BARD1 inhibition with DNA damage response therapies may offer enhanced treatment outcomes for pancreatic cancer patients.
Keywords:
BARD1DNA damagePARP inhibitorPancreatic ductal adenocarcinomac-Myc

More Related Videos

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

5.9K
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma06:21

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

Published on: November 19, 2019

10.9K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
3.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K