Our first joint endeavour with the organisation is to fund research into kidney related childhood cancers at Alder Hey Children’s Hospital.
Dr Bettina Wilm and her team will be investigating whether chemotherapy-induced senescence (the process of deterioration) affects the behaviour of stem cells in Wilms’ tumour. Wilms’ tumour is the most common kidney cancer in childhood, with up to 10 patients diagnosed in the North West of England every year.
With current therapy (chemotherapy, surgery and sometimes radiotherapy) most patient do well, but unfortunately 10-15% patients relapse with poor outcome. These patients need new drugs and approaches to treatment.
The biological mechanisms that allow cancer recurrence remain poorly understood. Relapse can be explained by the persistence of dormant (sleeping) residual cancer cells. Since relapse is the main cause of cancer-related death, understanding these dormant cells on a molecular level is essential for their eradication.
While most cells within a tumour are not capable of forming new tumours, rare cancer stem cells are able to generate tumours and become responsible for relapse and metastasis (when cancer spreads to a different body part). These cancer stem cells can be resistant to chemotherapy.
Chemotherapy and radiotherapy are known to induce cell senescence (ageing) in a proportion of tumour cells. Senescent cells have stopped dividing, and it was thought that they become permanently inactive. Recently it has been recognised that senescent tumour cells can escape senescence and turn again into active tumour cells. Furthermore, senescent cells are metabolically active and produce chemical signals which may promote tumour growth and increase stem cell numbers nearby, thus leading to relapse and metastasis.
Finding ways to eradicate the senescent cells with specific drugs may improve the treatment prospects for Wilms’ tumour patients. This is the first study to investigate therapy-induced senescence in pre-treated Wilms’ tumour and its relation to cancer stem cells.