Mechanisms of osteolytic and osteoblastic skeletal lesions

Lytic and blastic bone metastases represent extremes of a continuum, with most patients having a mixture of osteolytic and osteoblastic components in their lesions. This chapter provides the mechanisms responsible for osteolytic and osteoblastic metastasis, and also provides examples of how their identification has resulted in the development of new treatments for cancer in bone (CIB) patients. Multiple mechanisms contribute to tumor cells homing to bone and the subsequent development of bone lesions. Adhesion molecules expressed on tumor cells and cellular products from tumor cells also increase bone metastasis. In osteolytic metastasis and multiple myeloma (MM), the bone remodeling process is imbalanced, or uncoupled, with increased osteoclastic bone resorption driven by osteoclast-activating factors produced by the tumor cells, or by cells in the bone microenvironment in response to the tumor cells. Immune cell tumor cell interactions can suppress antitumor immune responses, and are an emerging therapeutic target for modulating the growth of tumors.