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BackgroundHsp90 is a chaperone protein that binds client proteinsinvolved in the regulation of cell survival and apoptosissignal transduction, including Akt, IKK complex, Apaf-1, survivin, CDKs, and KSHVvFLIP.Thisbindingisnecessary to maintain proper protein folding, assembly,transport, and function. A lack of Hsp90 results inprotein misfolding, ubiquitination, and degradation.KSHV vFLIP was identified as a viral gene that isresponsible for NF- B-dependent anti-apoptotic geneexpression in primary effusion lymphoma (PEL) cells[1]. In particular, the IKK signaling complex consistingof IKKa,IKKb,IKKg,vFLIP,andHsp90inthecaseofPEL cells was demonstrated as essential for survival inthese cells. As Hsp90 forms part of the IKK signalo-some in PEL cells, the Hsp90 inhibitor geldanamycinwas previously tested in these cells and has beenshown to inhibit activity of this complex in vitro. How-ever, geldanamycin is of limited therapeutic potentialdue to its undesirable pharmacophysiology. We testeda new purine-scaffold Hsp90 inhibitor with high selec-tivity for tumor versus normal cell Hsp90, which iswater-soluble with high oral bioavailability and excel-lent therapeutic window [2,3].Materials and methodsWe evaluated the sensitivity of several KSHV infectedand uninfected cell lines to treatment with this inhibi-tor, called PU-H71. We performed viability and NF- Breporter luciferase assays. Immunoblot analyses to cel-lularandviralproteinsweredonetoassesstheeffectof PU-H71. Finally, we used a mouse PEL xenograftmodel and in vivo imaging to assess tumor responsesto PU-H71.ResultsWe found all KSHV-positive PEL cell lines to be exqui-sitely sensitive when compared to uninfected lymphomacells, with growth inhibition at IC

Hsp90 is a viable therapeutic target in the treatment of KSHV-associated primary effusion lymphoma