Biology of Bone Metastases
Biology of Bone Metastases
Background: Bone metastases cause morbidity and mortality in multiple malignancies. In addition to portending a dire prognosis, bone metastases cause bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Improved understanding of the mechanisms that predispose tumor metastases to bone is needed to improve patients' therapeutic options, maintain their quality of life, and improve their survival.
Methods: This review discusses selected preclinical and clinical data regarding bone metastasis development and cytokine/molecular interactions predisposing to bone metastases formation. Potential interventions for reducing bone metastases are also described.
Results: Biologic mechanisms resulting in metastases of tumor cells to bone are being studied. Among these are the RANKL pathway, osteoclast activation via cytokines (produced by tumor cell and cells in the bone microenvironment), interactions with transient and stromal cells in the bone microenvironment, and molecules such as PTHrP and endothelin-1. These molecules offer important opportunities for targeted interventions to decrease bone metastases-associated morbidity.
Conclusions: Knowledge of the pathophysiology of bone and cancer is developing rapidly. Relationships among cancer cells, bone-derived cells, and cytokines provide opportunities for the development of new interventions. Therapy targeting osteoclast/osteoblast interactions has proven benefit for patients with bone metastases.
Approximately 70% of patients who die of breast or prostate cancer also have had bone metastases. Patients with kidney, thyroid, and lung cancers also have higher incidence of bone metastases compared with other types of cancers, such as gastrointestinal malignancies, which uncommonly spread to bone. In addition to portending a dire prognosis, bone metastases cause significant morbidity including bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Understanding the mechanisms that predispose tumor metastases to bone will improve the therapeutic options for patients, maintain quality of life, and perhaps improve survival. This review focuses on the mechanisms of bone metastases in breast cancer, prostate cancer, and multiple myeloma, as most of the existing research involves these diseases. However, it is important to note that other solid tumors, specifically lung, thyroid, and kidney, as mentioned above, have a relatively high incidence of bone metastases.
Approximately 30% to 65% of patients with metastatic lung cancers will develop bone metastases, as will approximately 47% of patients with advanced thyroid cancer and 30% of patients with advanced renal carcinoma. Bone metastases are a dire consequence and portend a poor survival, with a median of less than 6 months. The mechanisms involved in bone metastases of lung and other solid tumor malignancies include many of the same pathways, as discussed below.
Abstract and Introduction
Abstract
Background: Bone metastases cause morbidity and mortality in multiple malignancies. In addition to portending a dire prognosis, bone metastases cause bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Improved understanding of the mechanisms that predispose tumor metastases to bone is needed to improve patients' therapeutic options, maintain their quality of life, and improve their survival.
Methods: This review discusses selected preclinical and clinical data regarding bone metastasis development and cytokine/molecular interactions predisposing to bone metastases formation. Potential interventions for reducing bone metastases are also described.
Results: Biologic mechanisms resulting in metastases of tumor cells to bone are being studied. Among these are the RANKL pathway, osteoclast activation via cytokines (produced by tumor cell and cells in the bone microenvironment), interactions with transient and stromal cells in the bone microenvironment, and molecules such as PTHrP and endothelin-1. These molecules offer important opportunities for targeted interventions to decrease bone metastases-associated morbidity.
Conclusions: Knowledge of the pathophysiology of bone and cancer is developing rapidly. Relationships among cancer cells, bone-derived cells, and cytokines provide opportunities for the development of new interventions. Therapy targeting osteoclast/osteoblast interactions has proven benefit for patients with bone metastases.
Introduction
Approximately 70% of patients who die of breast or prostate cancer also have had bone metastases. Patients with kidney, thyroid, and lung cancers also have higher incidence of bone metastases compared with other types of cancers, such as gastrointestinal malignancies, which uncommonly spread to bone. In addition to portending a dire prognosis, bone metastases cause significant morbidity including bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Understanding the mechanisms that predispose tumor metastases to bone will improve the therapeutic options for patients, maintain quality of life, and perhaps improve survival. This review focuses on the mechanisms of bone metastases in breast cancer, prostate cancer, and multiple myeloma, as most of the existing research involves these diseases. However, it is important to note that other solid tumors, specifically lung, thyroid, and kidney, as mentioned above, have a relatively high incidence of bone metastases.
Approximately 30% to 65% of patients with metastatic lung cancers will develop bone metastases, as will approximately 47% of patients with advanced thyroid cancer and 30% of patients with advanced renal carcinoma. Bone metastases are a dire consequence and portend a poor survival, with a median of less than 6 months. The mechanisms involved in bone metastases of lung and other solid tumor malignancies include many of the same pathways, as discussed below.
