ECE2019 Symposia Cancer drug-induced osteoporosis (Endorsed by Endocrine Connections) (3 abstracts)
Germany.
Skeletal lesions are a frequent complication of breast and prostate cancer. At present, 6080% of patients with breast or prostate cancer develop bone metastases, which frequently result in skeletal-related events, including pathological fractures, pain, and neurological syndromes that require surgery or radiotherapy, and reduce quality of life. Autocrine and paracrine factors modulate various aspects of bone metastasis, including tumor proliferation, epithelial-to-mesenchymal transition, sensitization of skeletal sites to tumor homing, instruction of the microenvironment to support tumor persistence, and initiation of a vicious cycle that further promotes tumor growth and survival. In the vicious cycle, tumor cells, in particular breast cancer cells, produce osteoclast-stimulating cytokines and growth factors, either directly or by enhancing their production by mesenchymal stromal cells. This process results in excessive bone destruction that is typical of osteolytic bone metastases. However, it also releases large amounts of locally stored growth factors from the bone matrix that serve as survival factors for tumor cells. More recently, osteogenic pathways have been implicated in the development of bone metastasis. Normal bone formation depends on osteogenic differentiation of mesenchymal stromal cells towards osteoblasts and later to osteocytes. Tumors such as breast cancer secrete e.g. the Wnt inhibitor DKK-1, which suppresses osteoblast differentiation and inhibits bone formation and repair. By contrast, prostate cancer cells produce growth factors, which act as local stimulators of osteoblast functions, contribute to the osteomimicry phenotype of prostate cancer, and lead to excessive, but unorganized, newly formed bone, the hallmarks of osteosclerotic bone metastases. Taken together, prostate and breast cancer use specific molecular setups to induce their hallmark-type of bone lesion. Understanding the underlying mechanisms will help develop targeted therapies to treat bone metastasis.