Metastatic spread to bone: The role of chemotherapy

Cancer metastasis includes tumor cell intravasation, transport and immune evasion within the circulatory system, arrest at a secondary site, extravasation and finally, colonization and growth [1]. However, cancer metastasis remains poorly understood in terms of clinical outcome, pathology and tissue specificity of different tumor types. The predilection of some cancers to target and proliferate in bone is also unclear (Figure 2.1). Less than 1% of cancer cells entering the blood circulation successfully generate metastatic foci [2]. Consequently, there are few successful treatments that directly target metastatic cancer; identifying effective therapeutic targets for this stage of cancer and prognostic factors to identify those patients prone to develop local and distant progressive disease is challenging [2].

Genetic profiling of tumors has revealed important regulators of the metastatic process and suggested novel targets for cancer therapeutics. Targeting the tumor cell alone is not sufficient; multimodality therapy against tumor cells, their growth factors and the essential accessory cells with which cancer cells interact is imperative. In the bone marrow and within the tumor stroma, two niches constitute highly specific, physiologically defined sites; the vascular and stromal niche. A high preponderance of tumor cells is found in the bone marrow of patients with malignancy, even in the absence of overt distant metastases. Bisphosphonates inhibit normal and pathologic osteoclast-mediated bone resorption. Denosumab inhibits the maturation of osteoclasts by binding to RANKL, protecting the bone from degradation.