Most cancer patients are not killed by their primary tumors but succumb to metastatic disease. The most common human cancers--lung, breast, and prostate--frequently spread to bone, causing suffering and morbidity through pain, fractures, and nerve compression syndromes.
Tumor cells enter bones through blood and lymphatic vessels. In order to establish bone metastases, they have to influence bone metabolism. Most breast cancers that spread to bone express high levels of parathyroid hormone related protein, or PTHrP, a molecule that promotes bone breakdown. Scientists believe that the bone breakdown caused by PTHrP starts a vicious cycle: cross-talk between the tumor cells and the osteoclasts, cells that specialize in breaking down bone, ultimately leads to more and more bone loss and more and more aggressive growth of the tumor.
Consistent with this scenario, inhibition of osteoclast activity not only decreases bone lesions but also reduces tumor burden in animals. Preliminary results from human patients treated with bisphosphonates, a group of drugs also used to prevent and treat osteoporosis, suggest that the same might be true in humans.
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