Targeting of therapeutic agents to bone to treat metastatic cancer

The three main organs affected by metastasis of all cancers include lungs, liver, and bone. Clinical confirmation of tumor spread to these organs is a negative prognostic sign that marks the stage when disease is rarely curable. Today, treatment of bone metastases is primarily palliative. The aims of treatment are to relieve pain, prevent development of pathologic fractures, improve mobility and function, and if possible, prolong survival. Significant improvements in our understanding of tumor biology along with early tumor detection has led to the discovery of few innovative approaches aimed to treat bone metastases. The most promising treatment modalities include combination of anti-cancer therapies (surgery, radiation therapy, citostatic therapy) with bone antiresorptive therapies (bisphosphonate) that specifically target osteoclasts, bone resorbing cells. The osteoclast, whose increased activity is induced by the tumor, is responsible for the deterioration of bone mass and structure along with the release of grow factors that feed back and support further tumor growth. The current pharmaceutical approach is to target bone metastases by developing drugs that specifically target tumor cells in bone in addition to bone stroma since skeletal metastases are more resistant to treatment, present the highest bulk of tumor mass in the body, serve as site for secondary spread of tumor cells, and are associated with significant morbidity. There is a real need for a more effective modified release of newer anti-cancer drugs such as gene therapy and immunotherapy by using established and novel delivery platforms that will improve therapy and reduce side effects as a result of more appropriate plasma profiles. Overall, however, developments regarding treatment of cancer metastases to bone are encouraging. The scope of future advancements is immense and includes innovative therapeutics and delivery systems aimed to improve skeletal affinity, selectivity, and efficacy of drugs. (c) 2005 Elsevier B.V. All rights reserved.