Dedicator of Cytokinesis 4: A Potential Prognostic and Predictive Biomarker Within the Metastatic Spread of Breast Cancer to Bone

Abstract

Metastasis to bone occurs in over 70% of patients with advanced breast cancer resulting in skeletal complications, including pathological fractures, hypercalcaemia, and bone pain. Significant advances have been made in the treatment of bone metastases, including the use of antiresorptive drugs, such as bisphosphonates, as well as antibody-based therapies targeting key signalling intermediates within the process of cancer-mediated bone destruction. Despite these advances, treatment is not without side effects, including osteonecrosis of the jaw therefore biomarkers predictive of which patients are at high risk of developing bone spread are required to enable personalized medicine initiatives within this important disease area. We used proteomic analysis to compare the protein expression within (1) a parental triple negative human breast cancer cell line, (2) a fully bone homing cell line and (3) a lung homing cell line. The bone and lung homing cell-lines were derived by intra-cardiac injection of fluorescently labelled cells within immune-compromised mice. Proteomics identified Dedicator of Cytokinesis 4 as a biomarker predictive of bone spread, and this finding was further supported by the observation that high levels of Dedicator of Cytokinesis 4 within primary breast tumours were predictive of breast cancer spread to bone. Here, we provide an overview of this study and put the findings into context.