In the Netherlands, colorectal cancer (CRC) is one of the most common and deadly forms of cancer. Despite advances in precision medicine, the prognosis for patients with advanced CRC remains poor, highlighting the urgent need for new treatments.
The “dark genome”: a largely unexplored territory
A promising but still under-researched direction is the so-called “dark genome.” This includes long non-coding RNAs (lncRNAs) and microproteins, which, due to their unique properties, offer new opportunities for targeted therapies.
Research team receives ZonMW grant
Led by Nicolas Leveille (Amsterdam UMC) and Sebastiaan van Heesch (Princess Máxima Center), the team is investigating the role of the dark genome in colorectal cancer with support from ZonMW. They systematically assess the functionality of all annotated lncRNAs and microproteins across different CRC subtypes, using RNA-focused and CRISPR-based screening methods.
Microproteins and new treatment possibilities
“A central goal is to discover which parts of the dark genome are translated into functional microproteins, to reveal their contribution to colorectal cancer, and to use this knowledge for new therapies,” says Sebastiaan van Heesch. “Microproteins are largely unknown, but may play an important role in tumor biology and treatment response. By systematically characterizing them, we hope to find new biomarkers and therapeutic targets.”
Expanding knowledge and new strategies
“With the support of ZonMW, we can expand our understanding of the dark genome and translate this into applicable strategies for improved treatment,” says Nicolas Leveille. “This research enables us to investigate both the coding and non-coding roles of lncRNAs, an important and often overlooked issue.”
The project focuses on identifying new biomarkers and therapeutic targets, with the aim of improving the treatment of colorectal cancer.