While relatively non-toxic, our preclinical findings suggest that survivin inhibition is a promising therapeutic approach for MCVpositive MCC. For MCC xenografts, regression, growth rate, and even metastatic escape are highly cell line dependent. Liver metastasis was only observed with MKL-1 xenografts, and metastasis was only observed after survival was significantly prolonged with YM155 treatment. While WaGa does not undergo regression or even tumor shrinkage upon YM155 treatment, survival was significantly prolonged relative to saline treatment owing to a reduced tumor growth rate. Why MCC xenografts stop responding to YM155 treatment and what determines overall response to YM155 for a given MCC cell line remains unknown. Previous studies using MCV-positive MCC cell lines identified CP-358774 183319-69-9 bortezomib as a potent in vitro chemotherapeutic, but not in vivo. Topoisomerase type I and type II inhibitors were also shown to induce death of MCC cell lines. Although we again verified in vitro efficacy of bortezomib, etoposide, and topotecan, none of these agents act synergistically with YM155 treatment��the effect is only additive. However, this may not exclude the possibility that combination therapy of topoisomerase inhibitors with survivin inhibitors will prove beneficial in future studies. Eukaryotic DNA is assembled into chromatin, the repeating structure of which is known as the nucleosome. Chromatin encodes epigenetic information and is important in regulating gene transcription, DNA repair and high throughput screening replication. Chromatin is subject to regulation by post-translational modifications such as methylation, acetylation, phosphorylation and ubiquitylation of histones, which are the protein structural component of the nucleosome. Histone acetylation can alter chromatin structure and also recruit additional protein machinery involved in chromatin regulation. Histone acetylation is catalyzed by lysine acetyltransferases, which catalyze the transfer of an acetyl group from acetyl-CoA to e-amino groups on specific histone lysine residues. The catalytic activity of Rtt109 is subject to complex regulation. In the absence of autoacetylation or the chaperone proteins Asf1 or Vps75, S. cerevisiae Rtt109 has lower KAT activity. Vps75 is a member of the NAP1 histone chaperone family and forms a stable complex with Rtt109 in vivo and in vitro. Opportunistic fungal infections can severely compromise the therapeutic outcome of cancer patients, organ transplant patients and other immunocompromised patients. The crude mortality rate from opportunistic fungal infection exceeds 50% in many human studies.