Efficacy of phosphatidylinositol-3 kinase inhibitors in a primary mouse model of undifferentiated pleomorphic sarcoma.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kim, S; Dodd, RD; Mito, JK; Ma, Y; Kim, Y; Riedel, RF; Kirsch, DG

Published Date

  • 2012

Published In

Volume / Issue

  • 2012 /

Start / End Page

  • 680708 -

PubMed ID

  • 22619567

Pubmed Central ID

  • PMC3350993

Electronic International Standard Serial Number (EISSN)

  • 1369-1643

Digital Object Identifier (DOI)

  • 10.1155/2012/680708


  • eng

Conference Location

  • Egypt