Translational Research > Paediatric Cancer Biology

Brain tumours (medulloblastoma, glioblastoma and rhabdoid tumours)
Central nervous system tumours are the most common group of solid tumours in childhood and are the leading cause of cancer-related death in this age group. The challenge is not only to increase survival, but also to improve the quality of life of survivors by decreasing the toxicity of the treatment which at present is substantial. Medulloblastoma is the most common malignant brain tumour in childhood. Very young children and those with disseminated tumour (metastatic) at diagnosis have a particularly poor prognosis. Standard treatment consists of surgery to remove as much of the tumour as possible followed by radiotherapy to the whole head and spine and chemotherapy. At all ages, treatment including craniospinal irradiation is associated with significant long term side effects including often devastating intellectual impairment, growth delay and endocrine abnormalities. We have observed different sensitivity of medulloblastoma cells to chemotherapeutic treatment depending on their genomic signature (mutations in different genes). From this observation we want to discover the major cellular molecules that need to be targeted to achieve optimal killing of cancer cells.

Rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of adolescence and childhood and accounts for 5% of all malignant paediatric tumours. Of the two major histological subtypes, alveolar RMS (ARMS) is more aggressive, has a significantly worse outcome, and is more frequently associated with bone marrow spread than embryonal RMS (ERMS). Normally, CXCR4, a cell receptor specifically binds to a molecule called SDF-1/CXCL12), and regulates how white cells home into the bone marrow. Tumours have hijacked this system increasing the regulation of CXCR4 and using it to form metastases, (tumour spread) and it has been shown that bone marrow metastasis of RMS involves the SDF-1/CXCR4 axis. Another molecule, b-catenin, is a multifunctional nuclear messaging factor in the Wnt signalling pathway, which is actively involved in forming muscle.  Dysregulation of Wnt/b-catenin signalling has been shown to facilitate cancer invasion and metastasis in various tumours. How these molecules contribute to the formation and dissemination of tumour metastases is the focus of present work.