PhD projects for research students
Bone related cancers are common and represent a wide spectrum of malignant disease. Radium-223 (223Ra) is a form of ionising radiation which selectively targets to bone-cancer sites where it very effectively causes the malignant cancer cells to die. The success of this new therapy in improving patient survival in prostate cancer patients is creating a great deal of excitement whereby its therapeutic use may be broadened to include other cancers with bone disease including those in younger patients. Immature blood cells, which mature into all of the different cell types of the peripheral blood, reside in the bone marrow (BM). Immature blood cells therefore sit close to radioactive-targeted cells of the bone which means that they are potentially at risk of radiation exposure as a consequence of this treatment. To date, the risks of such exposure on long-term BM complications such as secondary, treatment-related leukaemia are unknown.
Key objectives of the proposed research are (i) whether cells of the haemopoietic system are directly (or indirectly) exposed to 223Ra upon uptake into bone metastases and (ii), whether there is any evidence for the occurrence of radiation-induced genomic instability. These will be addressed in two ways. Firstly, whole blood will be sampled from prostate cancer (PCa) patients treated with 223Ra and secondly, we will irradiate a human 3D tissue culture model of BM in vitro. A range of cytogenetic techniques will be employed including multiplex fluorescence in situ hybridisation (M-FISH) to ascertain the frequency of transmissible radiation-induced chromosome aberrations. This will provide evidence of previous 223Ra (α-particle) exposure to the BM. Additional techniques employed may include the quantification of micronuclei, DNA damage foci and inflammatory cytokine secretion to examine for any radiation-induced bystander effect. Findings from this study will be used to determine whether 223Ra treatment results in any exposure to the BM and if so, to make estimations of the radiation dose and also, any potential long-terms risks of this.