Breast cancer bone metastases: pathogenesis and therapeutic targets

Current status and future directions in the treatment of bone metastases from breast cancer

“…1,6,[11][12][13] The picture emerging from these studies highlights the fact that bone colonization by malig- Figure 1). 1,[13][14][15] In particular, the bone marrow microenvironment appears to play a pivotal role in facilitating certain key steps in this process, including seeding, survival, dormancy and resistance of cancer cells to clinical treatment. [14][15][16] The complex interplay involving tumour cells, bone microenvironment and bone-resident cells, may, in part, explain the difficulty in identifying effective therapeutic approaches for preventing skeletal metastases or achieving a complete eradication of metastatic foci.…”

“…2,5,12 As the current therapeutic options are not shown to have a significant positive impact on patients' survival, in-depth knowledge of the biological mechanisms underlying the pathogenesis of bone metastasis may favour the development of new therapies that may be effective in improving the clinical outcome for these patients. 1,11 In this scenario, growing studies are specifically directed to deepen the patho-physiologic mechanisms fostering skeletal metastasis, that may pave the way to more effective therapeutic opportunities. 1,6,[11][12][13] The picture emerging from these studies highlights the fact that bone colonization by malig- Figure 1).…”

“…1,11 In this scenario, growing studies are specifically directed to deepen the patho-physiologic mechanisms fostering skeletal metastasis, that may pave the way to more effective therapeutic opportunities. 1,6,[11][12][13] The picture emerging from these studies highlights the fact that bone colonization by malig- Figure 1). 1,[13][14][15] In particular, the bone marrow microenvironment appears to play a pivotal role in facilitating certain key steps in this process, including seeding, survival, dormancy and resistance of cancer cells to clinical treatment.…”

“…[14][15][16] The complex interplay involving tumour cells, bone microenvironment and bone-resident cells, may, in part, explain the difficulty in identifying effective therapeutic approaches for preventing skeletal metastases or achieving a complete eradication of metastatic foci. 1,11,13 These observations suggest that effective treatment options to eradicate bone metastasis should rely on the combination of bonetargeted agents in association with different local and/or systemic antitumour treatment. 6,12,13,[17][18][19][20] This would entail a multidisciplinary approach involving medical oncologists, radiotherapists, orthopaedic surgeons, intervention radiologists and others.…”

“…6,12,13,[17][18][19][20] This would entail a multidisciplinary approach involving medical oncologists, radiotherapists, orthopaedic surgeons, intervention radiologists and others. 1,[11][12][13][17][18][19][20] Other pitfalls of current clinical treatment, in particular, treatment involving the systemic administration of antiresorptive drugs and/or antitumour agents and/or radiopharmaceuticals, include the negative effects exerted by these agents on the normal bone metabolism, which may result in detrimental consequences for cancer patients. 1,6,13,19,20 These findings indicate the need to develop novel therapeutic options that, based on the hallmarks of bone metastasis, can effectively thwart tumour cell growth while, at the same time, overcoming antitumour drug-induced bone loss and preserving bone health.…”