Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.
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PMID:Bone metastatic disease: taking aim at new therapeutic targets. 2165 83

Osteoporosis-pseudoglioma syndrome (OPPG; MIM 259770) is a very rare genetic disorder with an autosomal recessive mode of inheritance, characterized by congenital or infancy-onset visual loss and skeletal fragility, diagnosed during childhood. This syndrome can lead to severe disability and chronic bone pain. Low-density lipoprotein receptor-related protein 5 (LRP5) is the gene mutated and inactivated in OPPG, and plays a pivotal role in bone accrual and skeletal remodeling by controlling bone formation through activators, such as Wnt proteins, or inhibitors, such as DKK1. OPPG should be differentiated from osteogenesis imperfecta and child abuse by clinicians. Eye examination, coupled to bone phenotype and research of LRP5 mutation, are key points to diagnose OPPG. Chronic pain should be managed correctly in this syndrome with severe functional disability. Bisphosphonates allows fracture prevention, the catch-up of bone mineral density and improvement in mobility in children with OPPG. New drugs favoring osteoblast function and osteoclast inhibition are potential candidates in the treatment of OPPG.
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PMID:Treatment and management of osteoporosis-pseudoglioma syndrome. 3075