Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases

Abstract

Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone within these cancers. The application of molecular profiling techniques, together with animal model systems and engineered cell-lines has enabled the identification of a series of potential bone-metastasis biomarker molecules predictive of bone metastasis risk. Some of these biomarker candidates have been validated within patient-derived samples providing a step towards clinical utility. Recent developments in multiplex biomarker quantification now enable the simultaneous measurement of up to 96 micro-RNA/protein molecules in a spatially defined manner with single-cell resolution, thus enabling the characterisation of the key molecules active at the sites of pre-metastatic niche formation as well as tumour-stroma signalling. These technologies have considerable potential to inform biomarker discovery. Additionally, a potential future extension of these discoveries could also be the identification of novel drug targets within cancer spread to bone. This chapter summarises recent findings in biomarker discovery within the key bone metastatic cancers (breast, prostate, lung and renal cell carcinoma). Tissue-based and circulating blood-based biomarkers are discussed from the fields of genomics, epigenetic regulation (micro-RNAs) and protein/cell-signalling together with a discussion of the potential future development of these markers towards clinical development.

Development and Validation of a Predictive Model to Evaluate the Risk of Bone Metastasis in Kidney Cancer

“…The invasion of cancer cells requires roughly three processes: “escape” (malignant cells leave the kidney), “metastasis” (reaching the skeletal microenvironment suitable for mRCC growth via blood vessels), and “colonization” (formation of new lesions in the involved sites) ( 6 ). The metastasis tumor cells will invade the blood vessels and colonize in the target bone through a characteristic preference ( 27 , 28 ). Thus, predictors suggesting high malignancy of RCC still had efficacy in assessing BMs.…”

microRNA Prognostic Signature for Postoperative Success of Metastatic Orthopedic Cancers: Implications for Precision Microsurgery

“…miRNAs and their role in precision medicine, particularly with respect to bone metastasis, is increasingly being appreciated (Zoni and van der Pluijm, 2016;Wood and Brown, 2020). The overarching goal of this study was to evaluate if the miRNA signature can help predict the post-surgical outcome of patients with bone metastasis.…”

Transcriptome analysis of heterogeneity in mouse model of metastatic breast cancer

“…BM-derived cells expressed genes associated with BM metastases, including CEACAM1 and LCN2. (Sun et al, 2019;Westbrook et al, 2016;Wood & Brown, 2020) . Expression of CCL2, ADAMST1 and CXCR4 were also observed in BM-derived cells albeit to a lesser extent.…”