Targets in systemic molecular targeted therapies for bone metastases and their pharmacologic agents

Abstract

Tumor cells can secrete various cytokines which can enhance the activity of osteoclast in the bone microenvironment, and osteoclast can promote the release of many growth factors buried in bone matrix which would promote the growth and invasion of tumor cells. Thus, a ' vicious cycle' of bone destruction is developed in the bone metastatic microenvironment. Bone metastatic microenvironment facilitate this ' vicious cycle', while it also provides potential targets for the treatment of bone metastases. Osteoprotegerin, receptor activator of nuclear factor-κB and its ligand system are the typicality of molecular targets. Bone metastasis can promote the secretion of RANKL and the expression of OPG. The disbalance of RANKL/OPG is an important inducing factor for bone destruction. Many studies have shown that transforming growth factor-β which is produced by osteoclast plays an important role in mediating ' vicious cycle'. Src family tyrosine kinase, endothelin A receptor, matrix metalloproteinase, and cathepsin K are the potential targets of bone metastasis. Pharmacologic agents such as denosumab, can inhibit the ' vicious cycle' of bone metastasis. In addition to suppress bone destruction by Pharmacologic agents, they also can produce direct antitumor effect. They can delay the occurrence of skeletal related events, prolong the overall survival, and play an important role in patient's quality of life at last. Patients with bone metastasis have already benefited from systemic molecular targeted therapies, and further researches would be of great importance in improving patient therapeutically selections and enhancing the effect.