Efficacy of Phosphatidylinositol-3 Kinase Inhibitors in a Primary Mouse Model of Undifferentiated Pleomorphic Sarcoma
Joint Authors
Kim, Suzy
Mito, Jeffrey K.
Kirsch, David G.
Dodd, Rebecca D.
Ma, Yan
Kim, Yongbaek
Riedel, Richard F.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-04-29
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Recent advances in sarcoma genomics have identified novel mutations in the PI3K pathway in human sarcomas.
Here, we use a mouse model of primary soft-tissue sarcoma for preclinical testing of doxorubicin and inhibitors of the PI3K pathway: BKM120 (PI3K inhibitor) and BEZ235 (a dual PI3K/mTOR inhibitor).
Doxorubicin-treated tumors (n=15) showed a partial response rate of 6.6%, just as the majority of human sarcomas do not respond to doxorubicin.
Treatment with BKM120 elicited a partial response in 50% of tumors (n=10), which was also seen in combination with doxorubicin (n=10).
Additionally, BKM120 treatment produced a robust delay in tumor growth kinetics.
BEZ235-treated tumors (n=9) showed a complete response rate of 11.1%.
Combining BEZ235 with doxorubicin (n=10) increased the complete response rate to 50% (P=0.035).
These studies demonstrate that PI3K pathway inhibition is a viable and attractive target for soft-tissue sarcomas.
American Psychological Association (APA)
Kim, Suzy& Dodd, Rebecca D.& Mito, Jeffrey K.& Ma, Yan& Kim, Yongbaek& Riedel, Richard F.…[et al.]. 2012. Efficacy of Phosphatidylinositol-3 Kinase Inhibitors in a Primary Mouse Model of Undifferentiated Pleomorphic Sarcoma. Sarcoma،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-490002
Modern Language Association (MLA)
Kim, Suzy…[et al.]. Efficacy of Phosphatidylinositol-3 Kinase Inhibitors in a Primary Mouse Model of Undifferentiated Pleomorphic Sarcoma. Sarcoma No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-490002
American Medical Association (AMA)
Kim, Suzy& Dodd, Rebecca D.& Mito, Jeffrey K.& Ma, Yan& Kim, Yongbaek& Riedel, Richard F.…[et al.]. Efficacy of Phosphatidylinositol-3 Kinase Inhibitors in a Primary Mouse Model of Undifferentiated Pleomorphic Sarcoma. Sarcoma. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-490002
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-490002