Cancer Grand Challenge for research into unknown proteins
5 maart 2026
Research team ILLUMINE, which includes Dr. Sebastiaan van Heesch, has been awarded a prestigious Cancer Grand Challenge grant. The team is now starting an ambitious project to map proteins whose existence was unknown until recently. This ‘dark matter’ also includes the small microproteins in which Van Heesch specializes. These regulate certain processes in (cancer) cells that could form an important key to new therapies, including immunotherapy.
With the awarded Challenge, the team will have the resources to systematically map these stillmysterious proteins. When these proteins are present in cancer cells but not in healthy cells, the body’s own immune system may serve as the basis for immunotherapy, for example through cell therapy or a vaccine.
The international team consists of researchers from eight research institutions in four countries. Sebastiaan van Heesch, research group leader at the Princess Máxima Center and Oncode Institute, is eager to begin: ‘Together with the team, we are diving into an undiscovered world of new proteins whose existence was unknown until recently. We know they can be enormously important for how a cancer cell functions, but figuring out exactly how far this influence reaches and how we can translate this knowledge into successful new therapies is a tremendous challenge. It is an honor to take on this Cancer Grand Challenge with this team of experts.’
Team ILLUMINE, led by Reuven Agami of the Netherlands Cancer Institute (NKI), receives funding through the Cancer Grand Challenge from Cancer Research UK, the National Cancer Institute, the Cancer Research Institute, and Children Cancer Free Foundation (KiKa). Team ILLUMINE will receive up to 25 million US dollars over a period around five years. Today, it was announced that five teams are receiving funding through the Cancer Grand Challenges.
Dark proteome
Team ILLUMINE brings together experts with unique expertise in laboratory and clinical research and other components of the ‘dark proteome’. They are starting with the development of an atlas that maps various components of the full dark proteome of hardtotreat cancers. The team will do this for, among others, highgrade brain tumors and acute myeloid leukemia in children and adults, as well as ovarian, lung, and pancreatic cancer in adults.
The team uses technologies such as ribosome profiling, immunopeptidome profiling, and Tcell receptor analysis to gain insight into the origin and function of the ‘dark proteome’ in tumor biology. They are also investigating whether microproteins and other cancerspecific proteins generate new, potentially universal tumor antigens. These signaling molecules help the immune system recognize cancer cells and therefore offer leads for new therapies.
Van Heesch group
Sebastiaan van Heesch’s research group has already uncovered thousands of new microproteins. Van Heesch: ‘The human proteome is far more complex than previously thought. It resembles the ‘dark matter’ of proteins in cancer: a hidden world we barely understand, but which may have a major impact on how tumors arise and behave.’
Van Heesch expects that these proteins may play a key role especially in hardtotreat forms of childhood cancer. Earlier, the researchers already showed that medulloblastoma, a type of brain cancer, cannot survive without these proteins. In addition, many of these microproteins turn out to be highly tumorspecific, which could allow researchers to use them for new immunotherapies, such as cell therapy or vaccines. ‘I look forward to working with the team to explore how we can make the most of microproteins for adults and children with hard-to-treat forms of cancer.’
Would you like to learn more about team ILLUMINE? Visit the team page.