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Sunday, 03/24/2013 8:53:10 PM

Sunday, March 24, 2013 8:53:10 PM

Post# of 80490
Interesting AACR abtract from Dr. Druker Re: Ponatinib...

Found this one browsing the AACR abtracts for '113/Pona related content. Heavily edited by me below.



Abstract Number: 4971
Presentation Title: FGF2 promotes resistance to ABL kinase inhibitors in CML
Presentation Time: Wednesday, Apr 10, 2013, 8:00 AM -12:00 PM
Author Block: ......Brian Druker

Abstract Body: ...This screen identified Fibroblast Growth Factor 2 (FGF2) as a factor that mediates kinase inhibitor resistance in the CML cell line K562.... Inhibition of both FGFR and BCR-ABL in the FGF2 imatinib-resistant outgrowths was synergistic in promoting cell death.....Further evidence that FGFR may be important in kinase resistance is emerging from clinical trials of the novel ABL inhibitor, ponatinib. Although ponatinib was specifically developed to bind BCR-ABL with the T315I mutation, it is also a multi-kinase inhibitor, including inhibition of FGFR in the low nanomolar range. To wit, ponatinib was able to suppress FGF2 imatinib-resistant outgrowths in the low nanomolar range whereas imatinib, dasatinib and nilotinib were ineffective, even at high doses. In clinical trials, ponatinib has proven effective not only against T315I mutated BCR-ABL, but also in patients with minor or even no mutations of the ABL kinase domain (in press)...

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