2012
DOI: 10.1038/bcj.2011.44
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Inhibition of cell cycle progression by dual phosphatidylinositol-3-kinase and mTOR blockade in cyclin D2 positive multiple myeloma bearing IgH translocations

Abstract: Multiple myeloma (MM) is a clinically and genetically heterogenous cancer where tumour cells have dysregulated expression of a D-type cyclin, often in association with a recurrent IgH translocation. Patients whose tumour cells express cyclin D2, with the translocation t(4;14) or t(14;16), generally have more proliferative disease and inferior outcomes. The phosphatidylinositol-3-kinase (PI3K) pathway is a major regulator of D-type cyclin expression and cell cycle entry. We evaluated the effect of PI3K pathway … Show more

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Cited by 11 publications
(7 citation statements)
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“…They also indicate that this capacity should extend to upcoming drugs, such as the proteasome inhibitor carfilzomib and the IMiD pomalidomide. These data confirm and extend assessments recently made for broader PI3K inhibitors (Glassford et al , ; Munugalavadla et al , ) and for BYL‐719 (Azab et al , ), highlighting PIK3CA inhibition as the most promising means to achieve effective PI3K blockade while restricting the pharmacological effect to as specific a target as possible. Although it remains to be seen if comprehensive genetic information as will be available through modern sequencing techniques can stratify PIK3CA‐dependent versus ‐independent MM subgroups, the clinical testing of such inhibitors in combination with standard‐of‐care therapies appears highly warranted.…”
Section: Discussionsupporting
confidence: 88%
“…They also indicate that this capacity should extend to upcoming drugs, such as the proteasome inhibitor carfilzomib and the IMiD pomalidomide. These data confirm and extend assessments recently made for broader PI3K inhibitors (Glassford et al , ; Munugalavadla et al , ) and for BYL‐719 (Azab et al , ), highlighting PIK3CA inhibition as the most promising means to achieve effective PI3K blockade while restricting the pharmacological effect to as specific a target as possible. Although it remains to be seen if comprehensive genetic information as will be available through modern sequencing techniques can stratify PIK3CA‐dependent versus ‐independent MM subgroups, the clinical testing of such inhibitors in combination with standard‐of‐care therapies appears highly warranted.…”
Section: Discussionsupporting
confidence: 88%
“…Previous studies have demonstrated that BEZ235 inhibits proliferation and induces apoptosis in human myeloma cell lines and in primary MM PCs from some patients in vitro . Furthermore, BEZ235 treatment significantly reduced the subcutaneous growth of the human MM cell line MM1S in nude mice and induced a trend towards a decrease in tumour burden in a subcutaneous JIM1 tumour model in β 2 microglobulin null NOD/SCID mice .…”
Section: Discussionmentioning
confidence: 91%
“…Also, IGF1R, CCND2, and CCND1 also had been implied to be upregulated in MM [ 40 42 ] ; amplification of them was a significantly unfavorable parameter with regard to shorter overall survival [ 40 , 42 , 43 ] ; mechanism studies showed upon binding by IGF-1, IGF1R promoted the growth and migration of MM cells by activating the PI3K-Akt signaling pathway, [ 44 ] which subsequently upregulated cell cycle genes CCND2 and CCND1. [ 45 , 46 ] This signaling pathway was also enriched in our study by IGF1R and CCND1. In addition to these known target genes, our study also suggested CUL3 and ELAVL1 as underlying novel targets of miR-16 in MM.…”
Section: Discussionmentioning
confidence: 54%