A new study has revealed a hidden vulnerability in around half of all cancers - offering fresh hope for developing smarter, more effective treatments. The research, published in Nature Genetics, was led by Oncode Investigator Daniel Peeper at the Netherlands Cancer Institute and supported by Oncode Institute.
The key finding centers on a gene called CDS2, which plays a crucial role in the survival of many aggressive and treatment-resistant cancers. By targeting this gene, scientists believe they can selectively destroy cancer cells while leaving healthy ones unharmed.
Instead of starting with traditional lab experiments, Oncode Researcher Tim Arnoldus took a data-driven approach. He combed through massive genetic databases to search for what scientists call “Achilles’ heels” - weaknesses cancer cells can’t survive without. Through this analysis, he discovered a unique genetic relationship: in many cancers, another gene called CDS1 is switched off, making the cells highly dependent on CDS2 to stay alive.
When Arnoldus and his team blocked CDS2, cancer cells - especially those known to be aggressive and difficult to treat - quickly died, while healthy cells remained intact. These findings are particularly relevant for mesenchymal-like cancers, which tend to spread easily and resist conventional treatments. These tumors often arise when normal cells undergo a shift called epithelial-to-mesenchymal transition (EMT), and they account for about 50% of all cancer cases.
The researchers also discovered how CDS2 helps cancer cells survive: it supports the production of vital fat molecules. Without it, the cells build up toxic byproducts and eventually die. Excitingly, both computer models and lab experiments suggest that it may be difficult for cancer cells to develop resistance to this treatment strategy - a major hurdle in many current therapies.
While drugs that specifically block CDS2 don’t yet exist, the team is already working with medicinal chemists to develop them. “It will be challenging to selectively target CDS2 without affecting its close relative, CDS1,” says Peeper. “But early results give us confidence that it’s possible.”
This study is a powerful example of how computational biology - using big data to guide scientific discovery - can lead to new and unexpected ways to treat cancer. It may pave the way for more precise, less toxic therapies for some of the toughest cases in oncology.
The research was funded by the Oncode Institute and the KWF Dutch Cancer Society.