Development of Novel Anti-cancer Agents with Bone Anabolic Actions

In the bone marrow microenvironment, bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Multiple myeloma (MM) is the most frequent malignancy that involves bone and is characterized by extensive osteolytic bone destruction. MM cells induce osteoclastic bone resorption, and osteoclasts in turn enhance MM cell growth and survival, thereby forming a vicious cycle between bone destruction and myeloma expansion. Besides enhanced bone resorption, bone formation is suppressed in MM by factors derived from MM cells and bone microenvironment. However, despite of recent advances in the treatment of MM, MM still remains incurable, therefore, novel treatment modalities targeting bone disease are urgently wanted. In this review, I would like to show the role of p62-ZZ domain and Pim-2 in bone marrow microenvironment in MM, and the efficacy of inhibitors of these molecules as the bone anabolic actions in MM