An enzyme that blocks bone growth and spurs bone destruction may be a culprit behind cancer-driven bone disease, researchers say.
The findings in mice suggest that clinically approved inhibitors of the enzyme could potentially be repurposed for patients with multiple myeloma as well as breast, lung, and other solid tumors that metastasize to the bones. Bones are maintained by a tightly controlled balance between bone-building cells, known as osteoblasts, and bone-degrading cells called osteoclasts. Disruptions to this balance occur in multiple myeloma, where cancerous blood cells crowd the bone marrow, and in bone-metastatic tumors, which lead to chronic bone pain and fractures.
To better understand the mechanism underlying myeloma-induced bone disease, Huan Liu and colleagues analyzed samples from multiple myeloma patients and a mouse model of the disease. They found that myeloma cells produced large amounts of an enzyme called thymidine phosphorylase (TP) that correlated with more severe bone lesions in patients. TP triggered epigenetic changes in the expression of osteoblast as well as osteoclast differentiation-associated genes, leading to both blunted bone growth and bone breakdown.
Treating myeloma-bearing mice with TP inhibitors markedly reduced bone lesions, raising the possibility of repurposing these drugs to treat cancer-driven bone disease.
Article: Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma, Huan Liu, Zhiqiang Liu, Juan, Jin He, Pei Lin, Behrang Amini, Michael W. Starbuck, Nora Novane, Jatin J. Shah, Richard E. Davis, Jian Hou, Robert F. Gagel, Jing Yang, Science Translational Mediscine, doi: 10.1126/scitranslmed.aad8949, published online 24 August.