The project investigates certain cancer of the soft tissue or bone (soft tissue and bone sarcomas) that have a mutation in the retinoblastoma tumour suppressor protein (RB1). Mutations in RB1 are found in nearly 30% of the childhood forms of these cancers. Although soft tissue or bone sarcomas are overall rare cancers, they represent the 2nd highest cause of cancer death in children and young adults. New, more effective treatments with fewer side effects are urgently needed for these young patients.
Exploring retinoblastoma protein loss as an actionable target in paediatric bone and soft tissue sarcoma
Professor Sibylle Mittnacht
UCL Cancer Institute
12 February 2018
A specific group (roughly 30%) of these cancers, identified as having a mutation in RB1, lose a specific way to repair damage to their DNA. Cancers exploit DNA repair to survive cancer treatment, generally aimed at damaging DNA, and defective repair can make cancer cells more sensitive to anticancer medicines. The work proposed seeks to establish information concerning these issues, with the view to develop a therapy for these cancers that is more powerful, and less toxic.
Children with cancers in soft tissue and bone currently need to receive intense treatment in order to provide the best chance for them to be cured. While cure can be achieved today in more than half of the cases, there are severe and sometimes life changing side effects associated with the treatment, and survival has remained uncertain in too many cases.
The work proposed will provide information that can be used to improve therapy for a sizeable group of children and young adults with sarcoma. In the first instance, producing molecular evidence to identify optimal medicine combinations, and by identifying new routes based in specific dependencies that the team believe exist the cancer cells in order for them to survive molecular damage to their DNA.
Professor Sibylle Mittnacht is a Professor in Cancer Biology leading a research team at the UCL Cancer Institute. Professor Mittnacht and her team have been working to understand the function of RB1, which is mutated in a considerable portion of childhood bone and soft tissue sarcoma for a long time.
In this project, Professor Mittnacht will work closely with Dr Sandra Strauss, a cancer doctor who treats children and young adults with bone and soft tissue cancers, to ensure the study is designed to maximise clinical relevance and provide important materials.
There are two other collaborators, Dr Paul Huang, from the Institute of Cancer Research, who is an expert in the analysis of sarcoma at the molecular level and Prof Penelope Jeggo, from the Genome Damage Centre at Sussex University who is an expert in studying the repair of DNA damage in cells. They will help with the study design and make sure the work progresses as fast as it can.
There are a number of different types of treatment used for childhood cancer including surgery, chemotherapy, radiotherapy, immunotherapy, stem cell transplantation and Precision Medicine. Often a combination of these treatments is used.Read more
The survival rate for children affected by tumours like paediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) remains low, and we urgently need new treatments.Read more