Osteoclast‐targeting small molecules for the treatment of neoplastic bone metastases
- 11 October 2009
- journal article
- review article
- Published by Wiley in Cancer Science
- Vol. 100 (11), 1999-2005
- https://doi.org/10.1111/j.1349-7006.2009.01294.x
Abstract
Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors.Keywords
This publication has 54 references indexed in Scilit:
- Emerging treatments for postmenopausal osteoporosis – focus on denosumabClinical Interventions in Aging, 2009
- Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systemsNature Reviews Immunology, 2007
- Molecular Mechanisms of Action of Bisphosphonates: Current StatusClinical Cancer Research, 2006
- The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugsProceedings of the National Academy of Sciences of the United States of America, 2006
- Bisphosphonates for malignancy-related bone disease: current status, future developmentsSupportive Care in Cancer, 2006
- Mechanisms of Bone MetastasisThe New England Journal of Medicine, 2004
- Osteoclast differentiation and activationNature, 2003
- Metastasis to bone: causes, consequences and therapeutic opportunitiesNature Reviews Cancer, 2002
- Reaching a Genetic and Molecular Understanding of Skeletal DevelopmentDevelopmental Cell, 2002
- Therapeutic Approaches to Bone DiseasesScience, 2000