Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past decade, our understanding of the molecular mechanisms that underlie breast cancer pathology and progression has dramatically improved. Using this knowledge, we have identified additional targets and developed novel therapeutic interventions in breast cancer. Together, these translational research efforts are helping to usher us into an age of personalized cancer therapy. Metastasis to bone is a common and devastating consequence of breast cancer. Bisphosphonates, which represent the current gold standard in bone metastasis therapies, are being improved with newer and more efficacious generations of these compounds being developed. Breast cancer growth in the bone requires activation of various signaling pathways in both cancer cells and stromal cells, including those that are stimulated by TGF-beta and RANKL, and mediated through the Src tyrosine kinase. Bone cells and cancer cells alike express promising targets for therapeutic intervention, including Cathepsin K, CXCR4 and GPNMB. In this article we discuss the molecular mechanisms behind these pro-metastatic molecules and review the most recent findings in the clinical development of their associated targeted therapies.
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PMID:Emerging therapeutic targets in breast cancer bone metastasis. 2002 Dec 9

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