In osteolytic bone metastases, multiple cytokines and growth factors secreted by tumor cells, such as PTHrP, RANKL, interleukins, prostaglandin E, tumor necrosis factor (TNF), and macrophage colony stimulating factor (MCSF), are responsible for hyperactive osteoclast activity, leading to osteoclast bone resorption and promoting osteolytic metastasis (59, 61, 62). The gene discussed is TNF; the disease is neoplasm.