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The PI3K\/Akt\/<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> pathway mediates proliferation, survival and drug resistance in MM plasma cells and is also involved in regulating the formation and activity of bone\u2010forming osteoblasts and bone\u2010resorbing osteoclasts. NVP\u2010BEZ235 is a dual pan class I PI3K and <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> inhibitor that is currently undergoing clinical evaluation in several tumour settings. In this study, we examined the anti\u2010tumorigenic effects of <jats:styled-content style=\"fixed-case\">BEZ<\/jats:styled-content>235 in an immunocompetent mouse model of MM and assessed the effects of BEZ235 on osteoblast and osteoclast formation and function. BEZ235 treatment (50\u00a0mg\/kg) resulted in a significant decrease in serum paraprotein and tumour burden, and <jats:italic>\u03bc<\/jats:italic>CT analysis of the proximal tibia revealed a significant reduction in the number of osteolytic bone lesions in BEZ235\u2010treated animals. Levels of the serum osteoblast marker P1NP were significantly higher in BEZ235\u2010treated animals, while levels of the osteoclast marker TRAcP5 were reduced. <jats:italic>In vitro<\/jats:italic>, BEZ235 decreased MM plasma cell proliferation, osteoclast formation and function and promoted osteoblast formation and function. These findings suggest that, in addition to its anti\u2010tumour properties, BEZ235 could be useful in treating osteolytic bone disease in MM patients.<\/jats:p>","DOI":"10.1111\/ejh.12436","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T05:47:59Z","timestamp":1409636879000},"page":"343-354","source":"Crossref","is-referenced-by-count":29,"title":["The effect of the dual PI3K and <scp>mTOR<\/scp> inhibitor BEZ235 on tumour growth and osteolytic bone disease in multiple myeloma"],"prefix":"10.1111","volume":"94","author":[{"given":"Zhen Ying","family":"Gan","sequence":"first","affiliation":[{"name":"Myeloma Research Laboratory School of Medical Sciences University of Adelaide Adelaide SA"},{"name":"Centre for Stem Cell Research Robinson Institute and Centre for Personalised Cancer Medicine University of Adelaide Adelaide SA"},{"name":"School of Pharmacy and Medical Sciences University of South Australia Adelaide 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