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

Bone lesions are a prominent feature accompanying multiple myeloma. Elucidation of the mechanisms regulating osteolysis is crucial in achieving a good quality of life, as such patients suffer from bone pain even after achieving improvement of the disease by high-dose chemotherapy. Recent research has revealed that bone lysis in myeloma patients is the result of both inhibited bone formation and enhanced bone destruction. It has been considered that bone absorption is regulated by activation of osteoclasts mediated by osteoclast activating factor (OAF) produced from myeloma cells. Macrophage inflammatory protein-1 alpha (MIP-1a) is a member of the chemokine family, and was originally determined as a soluble factor secreted from activated macrophages. Many candidates for OAF had been proposed and MIP-1a is now considered a major OAF. In this review, the significance of MIP-1a in myeloma bone disease is summarized.
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PMID:Bone lesions and macrophage inflammatory protein-1 alpha (MIP-1a) in human multiple myeloma. 1601 47

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