IMPROVING THE EFFECTIVENESS OF RADIOTHERAPY IN CERVICAL CANCER: TARGETING THE CXCL12 PATHWAY TO INCREASE TUMOUR CONTROL

The CXCL12/CXCR4 pathway has been shown to promote tumour growth, metastasis and radiochemotherapy resistance in many tumour sites, including in cervical cancer. We hypothesized that the addition of the CXCR4 inhibitor Plerixafor to radiochemotherapy would result in longer tumour growth delay and potentially improve tumour control compared to radiochemotherapy alone, without added toxicity. Two primary orthotopic cervical cancer xenograft models were implanted in the cervices of mice and treated with radiochemotherapy with/without Plerixafor. The addition of Plerixafor to radiochemotherapy resulted in a trend for higher local tumour control in one tumour model, and in faster tumour regression in both tumour models, without evidence of added toxicity. In the late intestinal toxicity study, there was a trend for lower toxicity in mice receiving radiochemotherapy + Plerixafor arm compared to radiochemotherapy. Our work suggests that the addition of Plerixafor to radiochemotherapy results in better primary tumour control, without added toxicity.%%%%M.Sc.