Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer
en-GBde-DEes-ESfr-FR

Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer

06/11/2024 Frontiers Journals

A novel discovery in the field of pancreatic cancer treatment has been unveiled, revealing the epigenetic silencing of BEND4 as a potential synthetic lethal marker for enhancing the efficacy of ATM inhibitors in pancreatic cancer treatment. This innovative research provides a groundbreaking approach to targeting a tumor suppressor gene, BEND4, which is frequently methylated and silenced in pancreatic cancer. The study delves into the role of BEND4 in DNA damage repair and its potential as a therapeutic marker when combined with ATM inhibitor treatment.

The investigation was conducted using a comprehensive methodology, including cell line experiments, tissue sample analysis, and in vivo studies. The researchers evaluated the expression and methylation status of BEND4 in various pancreatic cancer cell lines and tissues, finding a significant association between BEND4 methylation and poor tumor differentiation. Furthermore, BEND4 methylation was identified as an independent poor prognostic marker for patients with pancreatic ductal adenocarcinoma (PDAC).

The study demonstrated that BEND4 suppresses cell growth, induces G1/S arrest and apoptosis, and inhibits migration and invasion in PDAC cells. The underlying mechanism involves BEND4's interaction with Ku80, a key player in the non-homologous end joining (NHEJ) pathway, which is a major DNA double-strand break (DSB) repair pathway. The research showed that BEND4 overexpression enhanced the efficiency of NHEJ, while its knockdown reduced this efficiency, highlighting BEND4's role in DNA damage repair.

A pivotal finding of this research is the synthetic lethal effect when BEND4 expression is lost in combination with ATM inhibitor treatment. The study showed that PDAC cells with BEND4 methylation were more sensitive to the ATM inhibitor AZD0156, both in vitro and in vivo. This suggests that the epigenetic silencing of BEND4 can serve as a biomarker for predicting the response to ATM inhibitors in pancreatic cancer treatment.

The research also underscored the potential clinical implications of these findings. By targeting the ATM pathway in BEND4-silenced pancreatic cancer cells, a new therapeutic strategy could be developed. This strategy could lead to more effective treatments for patients with PDAC, particularly those with BEND4 methylation, offering a promising avenue for improving outcomes in a disease with historically poor survival rates.

In conclusion, this study presents a significant advancement in understanding the role of epigenetically silenced BEND4 in pancreatic cancer and its potential in enhancing the effectiveness of ATM inhibitor treatment. The findings provide a strong rationale for further research into the development of targeted therapies for PDAC, with a focus on exploiting the synthetic lethality between BEND4 methylation and ATM inhibitors. This research paves the way for more personalized and effective treatment approaches for patients with pancreatic cancer.
DOI: 10.1007/s11684-023-1053-3
Attached files
  • Fig 1
06/11/2024 Frontiers Journals
Regions: Asia, China
Keywords: Health, Medical

Disclaimer: AlphaGalileo is not responsible for the accuracy of news releases posted to AlphaGalileo by contributing institutions or for the use of any information through the AlphaGalileo system.

Testimonials

For well over a decade, in my capacity as a researcher, broadcaster, and producer, I have relied heavily on Alphagalileo.
All of my work trips have been planned around stories that I've found on this site.
The under embargo section allows us to plan ahead and the news releases enable us to find key experts.
Going through the tailored daily updates is the best way to start the day. It's such a critical service for me and many of my colleagues.
Koula Bouloukos, Senior manager, Editorial & Production Underknown
We have used AlphaGalileo since its foundation but frankly we need it more than ever now to ensure our research news is heard across Europe, Asia and North America. As one of the UK’s leading research universities we want to continue to work with other outstanding researchers in Europe. AlphaGalileo helps us to continue to bring our research story to them and the rest of the world.
Peter Dunn, Director of Press and Media Relations at the University of Warwick
AlphaGalileo has helped us more than double our reach at SciDev.Net. The service has enabled our journalists around the world to reach the mainstream media with articles about the impact of science on people in low- and middle-income countries, leading to big increases in the number of SciDev.Net articles that have been republished.
Ben Deighton, SciDevNet

We Work Closely With...


  • BBC
  • The Times
  • National Geographic
  • The University of Edinburgh
  • University of Cambridge
  • iesResearch
Copyright 2024 by AlphaGalileo Terms Of Use Privacy Statement