Examination of role of the CXCL12/CXCR4 cytokine pathway in human tumours treated with radiation with a focus on cancer of the cervix
Radiation is one of the primary modalities for the treatment of localized cancer and a number of factors can influence the response of tumours and surrounding normal tissues to such treatment. These factors, which can be specific to the individual tumour or normal tissue and to their environment, may vary from patient to patient. One part of our research focuses on understanding how the CXCL12/CXCR4 cytokine pathway affects tumour and normal tissue response to radiation treatment. Our work involves studies in PDX models of human cervix cancers orthotopically transplanted into immune-deprived animals in which we observe upregulation of this pathway and that blocking the pathway causes sensitization of radiation effects. We are currently extending this work to include spontaneously arising cervix cancers in immune-competent animals and to prostate cancer. Interestingly, blocking this pathway appears to reduce normal tissue (skin and GI-tract) response to radiation treatment so we are also examining the mechanisms for this effect. In these studies, we are collaborating with clinical groups at the Princess Margaret Cancer Centre to examine methods to measure gene expression and ablate this pathway and its potential to enhance anti-tumour immune mechanisms.