P N Munster

..These include HER2, p53 and Bcl-2, cathepsin B, p27, proliferating cell nuclear antigen (PCNA), cyclin D, Ki-67, and vascular endothelial growth factor (VEGF)...

..Ex vivo comet assays may be useful as a predictive tool when tumor cells are limited and serial biopsies are difficult to obtain...

..HCl) meets all of these criteria. This review summarises the development, preclinical studies and the clinical outcome of arzoxifene and places it in context with other modalities in the treatment of hormone receptor-positive tumours...

..These observations have important clinical implications because they may help to identify patients that are most likely to benefit from 17-AAG and may explain resistance to Herceptin as seen in many patients...

..These findings suggest that inhibition of Hsp90 function by 17-AAG enhances the apoptotic effects of cytotoxic agents. The sequence of drug administration and the RB status significantly influence efficacy...

..SAHA and other HDAC inhibitors are currently in Phase I clinical trials. These findings may impact the clinical use of these drugs...

..GMD-4c could be useful in the treatment of carcinomas dependent on HER-kinases...

..G1 arrest is sufficient for some but not all aspects of the phenotype. Induction of differentiation may be responsible for some of the antitumor effects of this drug...

..e. steroid receptors, Her2, Raf). We have used the structural features of this pocket to design a small molecule inhibitor of Hsp90...

..HCl-a novel, potent, third-generation selective estrogen receptor modulator (SERM)-because this benzothiophene derivative demonstrated an SERM profile in preclinical studies...

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..CONCLUSIONS: The recruitment of topoisomerase IIbeta as a target may overcome primary or emergent drug resistance to topoisomerase II-targeting agents and hence may broaden the applicability of this important class of anticancer agents...

..The proposed mechanism of action suggests an effect of drug sequencing on the antitumor activity of these drugs...

..These findings may impact the clinical development of combining HDAC inhibitors with DNA damaging agents...

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..The majority of women diagnosed with early-stage breast cancer have an excellent long-term prognosis, but many will undergo temporary or permanent chemotherapy-induced amenorrhea...

..Thus, pharmacological inhibition of Akt activation is achievable with ansamycins and may be useful for the treatment of HER2 driven tumors...

..The present study sought to determine whether fatigue was greater in women who had completed treatment for early-stage breast cancer relative to a demographically matched comparison group of women with no cancer history...

..To test the tolerability, safety, and recommended phase II dose of CP-724,714, a reversible, highly selective, oral HER2 tyrosine kinase inhibitor in patients with advanced solid tumor malignancies that express HER2...

..However, peripheral blood mononuclear cells may not be a predictive biological surrogate for drug-induced modulation of topo levels in tumor tissues and should be further explored in larger studies...

..CONCLUSIONS: In this retrospective review of patients treated at a single institution, those treated with multiagent chemotherapy but not with single-agent DTIC appeared to have had a survival benefit...

..Studies suggest that the period following completion of treatment can be distressing for cancer patients. One potentially important predictor of distress is physical symptoms/side effects during treatment...

..Finally, the utility of the topo II inhibitors could be enhanced if their efficacy could be increased without worsening toxicity, as our preclinical data appears to indicate. ..

..These findings may be useful in the rational design of future clinical trials involving HDACi. ..

..In pre- and post-treatment tumor samples, we will determine which HDACs are involved in the cellular effects induced by the HDACi and which HDACs may predict response. ..