Understanding how Wilms tumour stem cells escape chemotherapy

Wilms tumour is the most common kidney cancer in children. Treatments include chemotherapy and surgery to remove the cancer, which is generally successful. However, for about one in 10 children with Wilms tumour, the cancer grows back (relapses).

Researchers believe that a key reason for cancer relapsing is because some cancer cells are not killed during treatment. These survivors can adapt to resist chemotherapy, which then leads to the cancer growing back or spreading elsewhere in the body. One of the ways cancer cells survive is by becoming inactive, but these inactive cells can later re-activate. Researchers believe this is because the surviving cancer cells communicate with nearby cells following the end of chemotherapy.

Some re-activated cells can behave as cancer stem cells, which can produce lots of different types of cancer cell and may be responsible for cancer growth and relapse. These cancer stem cells, and other re-activated cells, are normally found within a specific region of the tumour called the ‘blastema’. When there are more chemotherapy resistant cells in the blastema in Wilms tumour, it is linked to a higher likelihood of relapse. The cancer stem cells may either lead to relapse in the kidney, or spread elsewhere like the lungs. However, doctors don’t know much about how those processes work.

Dr Bettina Wilm, at the University of Liverpool, wants to understand more about these processes, from communication and re-activation of cancer cells to how cancer stem cells behave. In this project, Dr Wilm will be studying cancer samples from Wilms tumour patients to explore every aspect of cancer stem cells, cells in the blastema and nearby cells that communicate with the cancer. This will involve looking at their behaviour, genetics, what molecules are present in the cell and how they interact with other cells.

This project will help doctors identify which Wilms tumours contain cancer stem cells and blastemal cells and are therefore potentially more likely to relapse. The different processes Dr Wilm’s team are investigating could also identify targets for new treatments that would help prevent relapse.