Bone Metastasis Mechanisms and Therapeutic Strategies

Bone metastasis is a multistep process in which cancer cells detach from a primary tumour, survive in the circulation, home to the skeleton and establish secondary lesions within the bone microenvironment. The “seed and soil” paradigm underlies the predilection of breast, prostate and lung carcinomas for bone, where tumour cells exploit interactions with osteoclasts and osteoblasts to drive either osteolytic or osteoblastic lesions. Key molecular mediators include receptor activator of nuclear factor-κB ligand (RANKL), cytokines such as interleukin-1β and parathyroid hormone-related peptide, and signalling pathways involving NF-κB, Wnt and TGF-β. Disseminated cells may enter a dormant state before reactivation, a process regulated by bone marrow stromal cells, extracellular matrix components and epigenetic modifiers. Therapeutic strategies aim to disrupt this vicious cycle through bone-targeted agents such as bisphosphonates, RANKL inhibitors and emerging small molecules that inhibit tumour–bone signalling axes. Preclinical models, including refined murine injection systems, continue to advance mechanistic insight and inform the development of adjuvant treatments designed to maintain dormancy, prevent skeletal-related events and improve quality of life.

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Bone Metastasis Mechanisms and Therapeutic Strategies publication trend

The graph below shows the total number of articles in bone metastasis mechanisms and therapeutic strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Metastasis: The spread of cancer cells from a primary tumour to distant organs, forming secondary growths.

Osteoclast: A specialised bone-resorbing cell that degrades mineralised matrix under the influence of RANKL and other factors.

Osteoblast: A bone-forming cell responsible for synthesis of the organic bone matrix and its subsequent mineralisation.

Bone microenvironment: The complex milieu of cells, extracellular matrix and soluble factors within bone that regulates homeostasis and metastatic colonisation.

Dormancy: A reversible state in which disseminated tumour cells survive in a non-proliferative phase, evading therapy and later reactivating.

Osteolysis: Pathological bone degradation driven by excessive osteoclast activity, often stimulated by tumour-derived signals.

References

1. Bone serves as a transfer station for secondary dissemination of breast cancer. Bone Research (2023).
2. Bone metastases: an overview. Oncology Reviews (2017).
3. Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials. Journal of Experimental & Clinical Cancer Research (2017).
4. A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries. Nature Communications (2018).
5. Molecular mechanisms and clinical management of cancer bone metastasis. Bone Research (2020).
6. Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling. Nature Communications (2019).