Omic-profiling in breast cancer metastasis to bone: implications for mechanisms, biomarkers and treatment

Despite well-recognised advances in breast cancer treatment, there remain substantial numbers of patients who develop metastatic disease, of which up to 70% involves spread to bone, resulting in skeletal complications which have a major negative impact on mortality and quality of life. Bisphosphonates and newer bone-targeted agents have reduced the prevalence of skeletal complications, yet there remains significant unmet clinical need, particularly for the development of more specific therapies for the prevention and treatment of metastatic bone disease, for the prediction of risk of its development in individual patients and for the prediction of response to treatments. Modern 'omic' strategies can potentially make a major contribution to meeting this need. Technological advances in the field of nucleic acid sequencing, mass spectrometry and metabolic profiling have driven progress in genomics, transcriptomics (functional genomics), proteomics and metabolomics. This review appraises the recent application of these approaches to studies of breast cancer metastasis (particularly to bone), with a focus on understanding how omic approaches may lead to new therapeutic options and to novel biomarker molecules or molecular signatures with potential value in clinical practise. The increasingly recognised need for rigorous sample quality control and both pre-clinical and clinical validation to meet the ultimate goals of clinical utility and patient benefit is discussed. Future directions of omic driven research in breast cancer metastasis are considered, in particular micro-RNAs and their role in the post-transcriptional regulation of gene function and the possible role of cancer-stem cells and epigenetic modifications in the development of distant metastases.