Professor Rob Mairs, University of Glasgow
Neuroblastoma is a cancer that mainly affects very young children. Patients whose neuroblastoma has spread at the time of diagnosis have a poor outlook; their disease is difficult to eradicate even with intensive treatment. This work aims to enhance the effectiveness of treatment by combining radioactive drugs currently used in neuroblastoma treatment with drugs that can sensitise neuroblastoma cells to radiation damage.
Amount of grant: £189,043 | Date of award: May 2015
Neuroblastoma is a cancer that arises in nerve tissue of infants and very young children. Although neuroblastoma may be present at the time of birth, it usually remains concealed until its growth impinges upon and affects the function of adjacent tissues.
In more than half of patients, neuroblastoma has metastasised by the time of diagnosis, spreading to the lymph nodes, bones, bone marrow, liver and skin. Such disease is difficult to eradicate, even with the most intensive drug regimes.
Although neuroblastoma responds to radiation treatment, widespread disease is difficult to treat because of the radiation damage that would be inflicted on normal organs. An alternative way of giving radiation treatment, using radioactive drugs that selectively target tumour cells, enables selective killing of the cancer throughout the body of the patient without harming normal tissue. In patients with advanced and aggressive disease the radioactive drugs alleviate pain and can bring about a lengthy remission but long-term cure is not achieved and patients eventually relapse.
Professor Mairs and colleagues aim to increase the cure rate by combining radioactive drugs with drugs called radiosensitisers which make the tumour more susceptible to radiation-induced damage.
They will compare the potency of two radioactive drugs (131I-MIBG and 177Lu-DOTATATE) alone, radiosensitisers alone and radioactive drugs and radiosensitisers in combination to see whether they can obtain benefit by combining the two treatments. These comparisons will be performed using experimental models of neuroblastoma and the team will assess the effects on tumour cells as well as toxicity to bone marrow. Those combination treatments that perform well will be further examined to understand the way in which the radioactive drugs co-operate with the radiosensitisers inside cancer cells.
The results of these studies will enable the team to determine the most suitable combination of treatments to apply to patients, taking into account the possibility of adverse effects on sensitive normal tissue such as bone marrow.
About the research team
This team has an excellent track record of translating basic science findings into clinical trials.
External reviewerThis work will be carried out within the Radiation Oncology Group of Professor Rob Mairs in the new, state-of-the-art Translational Cancer Research Centre at the University of Glasgow. The team has a strong track record in translating experimental therapeutic strategies into new treatments.
The results of Professor Mairs’ previous studies provided the rationale for current combination approaches to the treatment of neuroblastoma, pioneered by Dr Mark Gaze at University College London Hospital. Dr Gaze’s involvement in this study will ensure rapid clinical application of positive experimental findings.
What difference will this project make?
I am certain that this project will lead to combination therapies with possible clinical benefit that can be taken to the clinic.
External reviewerPredominantly, neuroblastoma is a disease of infancy. In patients whose tumour has metastasised, the disease is difficult to eradicate and patients have a very poor prognosis.
The radioactive drugs 131I-MIBG and 177Lu-DOTATATE are effective in controlling the growth of neuroblastoma without damaging normal tissues. However patients with advanced, aggressive disease are not cured by this or any other treatment.
Professor Mairs and colleagues believe that the greatest benefit will be gained by combining 131I-MIBG or 177Lu-DOTATATE with drugs that overcome the resistance of tumours to radiation. Their investigations will enable formulation of the most favourable blend of these radioactive drugs with radiosensitising drugs to combat neuroblastoma while minimising toxicity. Combination treatment will make the tumour more susceptible to the radioactive drugs. In this way, we hope it will be possible to improve the cure rate of neuroblastoma without adverse effects to the patients.
Read more: Neuroblastoma | Other neuroblastoma projects