KU Leuven study uncovers how breast cancer cells pause to survive chemotherapy — and how to target them
Scientists at KU Leuven have discovered that some breast cancer cells can survive chemotherapy by temporarily ‘shutting down’ in a way that mimics how embryos pause development under stress. The process is triggered by a specific signalling pathway — and by blocking it, researchers were able to prevent therapy resistance before it even started. The findings, accepted for publication in Cancer Research, could lead to more effective treatments for aggressive breast cancer types.
Triple-negative breast cancer is one of the most difficult forms of breast cancer to treat. Many patients respond well to chemotherapy at first, but the cancer often returns. This new study helps explain why: some cancer cells enter a kind of dormant state, making them temporarily invisible to treatment.
‘It seems like the cancer cells hit pause to ride out the storm,’ says Youssef El Laithy, PhD researcher at the Stem Cell Institute Leuven and first author of the study. ‘This behaviour is similar to a natural process seen in embryos — and now we know it can also be found in cancer cells.’
The paused cells — known as “persister” cells — don’t grow or divide while chemotherapy is active, but can wake up later, causing the tumour to start growing again. The researchers found that this pause is triggered by the WNT signalling pathway, a molecular communication system that tells cells when to grow, divide, or stay inactive. This pathway is crucial during early development but can also be hijacked by cancer.
Blocking the WNT pathway — specifically by preventing the release of WNT proteins that activate it — proved to be key. The researchers showed that combining chemotherapy with a WNT blocker stopped the formation of persister cells and made the treatment more effective.
To test this, the team used a combination of lab-grown tumour models, patient-derived organoids, and mouse experiments. They also analysed tumour samples from breast cancer patients during chemotherapy and found the same WNT-related patterns. This suggests that the findings are not just theoretical — they may also be relevant in real-world cancer treatment.
‘What makes this exciting is that we are not just targeting resistance — we are preventing it,’ says Professor Frederic Lluis Vinas, who led the study. ‘By understanding how these persister cells form, we can stop them before they gain a foothold.’
The project brought together several KU Leuven research teams, including those of Professors Christine Desmedt, Colinda Scheele, and Dr. Daniela Annibali. It also involved advanced imaging and screening platforms (TRACE and MOSAIC), and close collaboration with partners at the Netherlands Cancer Institute, Oncode Institute, and the Institute of Cancer Research in the UK.
Although more work is needed before these findings can lead to new treatments, the study reveals a promising way to make chemotherapy more effective — especially for patients with triple-negative breast cancer, who currently have limited treatment options.
More information:
Chemotherapy-Treated Breast Cancer Cells Activate the WNT Signaling Pathway to Enter a Diapause-Like Early Persister State, by El Laithy, Lluis et al. was published in Cancer Research.