Abstract
Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metastatic cancer cells. In order to improve the prognosis of patients with bone metastases this cycle must be broken. Radium-223 dichloride (radium-223), the first targeted alpha therapy (TAT) approved, is an osteomimetic radionuclide that is incorporated into bone metastases where its high-linear energy transfer alpha radiation disrupts both the activity of bone cells and cancer cells. Therefore, radium-223 treatment has been shown preclinically to directly affect cancer cells in both osteolytic breast cancer and osteoblastic prostate cancer bone metastases as well as to inhibit the differentiation of osteoblasts and osteoclasts. Clinical studies have demonstrated an increase in survival in patients with metastatic castration-resistant prostate cancer. Due to the effectiveness and low toxicity of radium-223, several novel combination treatment strategies are currently eliciting considerable research interest.
Highlights
Bone metastasis is commonly associated with significant clinical complications which cause severe decrease in quality of life due to pain, skeletal-related events, such as pathologic fractures and spinal cord compression, and reduced patient mobility [1,2]
The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly
In metastatic castration-resistant prostate cancer, bone metastases dominate the clinical picture of the disease, and bone metastasis has been shown to affect up to 90% of patients with mCRPC [8,9,10]
Summary
Bone metastasis is commonly associated with significant clinical complications which cause severe decrease in quality of life due to pain, skeletal-related events, such as pathologic fractures and spinal cord compression, and reduced patient mobility [1,2]. The presence of bone metastases is associated with a poor prognosis and reduced overall survival in both breast cancer and prostate cancer [3,4,5,6,7]. It is a recurring complication especially in prostate cancer, where bone is the primary site of metastatic disease [8]. In metastatic castration-resistant prostate cancer (mCRPC), bone metastases dominate the clinical picture of the disease, and bone metastasis has been shown to affect up to 90% of patients with mCRPC [8,9,10]. Multiple myeloma is clinically characterized by the infiltration of the bone marrow with differentiated plasma cells that cause lytic lesions in large bones and vertebrae
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