Authors: Chang Yang Deborah Veis Novack
Publish Date: 2013/06/06
Volume: 31, Issue: 5, Pages: 496-506
Abstract
The bone microenvironment is complex containing boneforming osteoblasts boneresorbing osteoclasts bonemaintaining osteocytes hematopoietic lineage cells as well as blood vessels nerves and stromal cells Release of embedded growth factors from the bone matrix via osteoclast resorption has been shown to participate in the alteration of bone microenvironment to facilitate tumor metastasis to this organ Many types of malignancies including solid tumors and leukemias are associated with elevated levels of inhibitor of apoptosis IAP proteins and IAP antagonists represent an important emerging class of anticancer agents IAPs exert antiapoptotic roles by inhibiting caspases and upregulating prosurvival proteins at least in part by activating classical NFκB signaling In addition IAPs act as negative regulators in the alternative NFκB pathway so that IAP antagonists stimulate this pathway The role of the classical NFκB pathway in IAP antagonistinduced apoptosis has been extensively studied whereas much less attention has been paid to the role of these agents in the alternative pathway Thus far several IAP antagonists have been tested in preclinical and early stage clinical trials and have shown promise in sensitizing tumor cells to apoptosis without significant side effects However recent preclinical evidence suggests an increased risk of bone metastasis caused by IAP antagonists along with potential for promoting osteoporosis In this review the connection between IAP antagonists the alternative NFκB pathway osteoclasts and bone metastasis are discussed In light of these effects of IAP antagonists on the bone microenvironment more attention should be paid to this and other host tissues as these drugs are developed further
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