Precision targeting of ecDNA-driven tumours through bioinformatic identification of synthetic lethal vulnerabilities

Using Network data to uncover new treatment targets for aggressive cancers 

Some cancer cells carry extra pieces of circular DNA called extrachromosomal DNA (ecDNA). Unlike the DNA in our chromosomes, these extra loops often contain genes that make cancers grow faster, resist treatment and return more aggressively, leading to poor outcomes for patients. 

To bring new hope to patients with ecDNA positive tumours, a research team led by Drs. Dave Cescon and Mitchell Elliott (Princess Margaret Cancer Centre) will use advanced bioinformatics tools and MOHCCN Gold Cohort data to identify weak spots in ecDNA-positive tumours that could be targeted by new or existing treatments. 

“Patients with ecDNA-positive tumours often do not respond well to current treatments and have a higher risk of their cancer coming back,” says Dr. Cescon. “We want to change that by finding specific vulnerabilities in these cancers that can be used to develop new therapeutic strategies.” 

Finding the cancer’s weak spots 

The project focuses on a concept called synthetic lethality, where blocking one gene makes a cancer cell die only if another gene is already altered. By scanning ecDNA-positive tumours for these gene pairs, the team hopes to uncover precise treatment targets that could lead to better therapies. 

By the end of the project, they aim to create a list of potential treatment targets for ecDNA-positive cancers, providing a roadmap for developing or repurposing drugs that exploit these vulnerabilities. The team will also share methods and results openly so other researchers can build on their work. 

“This work will help guide new approaches to treat patients whose cancers have been especially difficult to manage,” says Dr. Elliott. “Our goal is to translate discoveries into options that improve both survival and quality of life for patients.” 

A national effort driving precision oncology 

The team is one of the first five groups that will use aggregated data from the MOHCCN Gold Cohort for their research projects after being named recipients of the Network’s Data Sharing and Use Pilot program. Through this program, the team will not only show how shared national data can accelerate discoveries that benefit patients across Canada, but will also help validate the data access and sharing processes created by the Network, helping to ensure the process can be scaled in the near future. 

“By bringing together large-scale datasets, advanced analytics and teams across institutions, we are demonstrating the power of collaboration in precision oncology,” says Dr. Cescon. “This is exactly what the Marathon of Hope Cancer Centres Network was built to do.”