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|Title:||The Hsp90 inhibitor SNX-7081 synergizes with and restores sensitivity to fludarabine in chronic lymphocytic leukemia cells with lesions in the TP53 pathway: a potential treatment strategy for fludarabine refractory disease||Authors:||Forsyth, Cecily J ;Best, O.G.;Che, Y;Singh, N.;Christopherson, R.I.;Mulligan, S.P.||Issue Date:||Jul-2012||Source:||Volume 53, Issue 7, pp. 1367 - 1375||Journal title:||Leukemia & Lymphoma||Abstract:||Drug resistance in chronic lymphocytic leukemia (CLL) associated with lesions in the ATM/TP53 pathway represents a major challenge in clinical management. Evidence suggests that heat shock protein-90 (Hsp90) inhibitors may represent a therapeutic option in combination with more conventional therapies. We explored the effects of combining the Hsp90 inhibitor, SNX-7081, with fludarabine in vitro against CLL cells and hematological cell lines. In seven cell lines and 23 patient samples synergy between SNX-7081 and fludarabine (2-FaraA) was apparent in the three TP53 mutated cell lines and at significantly lower concentrations in TP53 or ATM dysfunctional patient cells. In 11/13 2-FaraA-resistant patient samples, SNX-7081 reduced the 50% inhibitory concentration to within a clinically achievable range. Synergy between SNX-7081 and 2-FaraA was evident in both the cell lines and patient samples as a significant decrease in cell viability. Our data suggest that combining SNX-7081 and fludarabine may be effective in the treatment of fludarabine-refractory CLL.||URI:||https://elibrary.cclhd.health.nsw.gov.au/cclhdjspui/handle/1/1268||DOI:||10.3109/10428194.2011.647310||Pubmed:||https://www.ncbi.nlm.nih.gov/pubmed/22149137||ISSN:||1026-8022||Publicaton type:||Journal Article||Keywords:||Cancer
|Appears in Collections:||Haematology|
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