However, persistent Stat3 activation has been shown to rescue tumor cells from sunitinib induced cell death and to promote cell proliferation by regulating genes encoding antiapoptotic and prolif eration associated proteins. selleck chemical Patients with brain metastases and activated Stat3 may require a treatment strategy that inhibits Stat3 in various ways. A combina tion of sunitinib with an anti interleukin 6 antibody has been suggested, since Stat3 activation is mediated by the interleukin 6 receptor. Another promising target whose Inhibitors,Modulators,Libraries expression correlates with advanced stage of dis ease is the chemokine receptor CXCR4, a key receptor in the crosstalk between tumor cells and their environ ment. In RCC, the loss of function of the Von Hip pel Lindau tumor supressor gene mediates up regulation of CXCR4 which then promotes tumor spread and progression.

The activity of CXCR4 directed agents has already been shown in animal tumor models and might be of particular interest in rapidly progressing tumors. Conclusions Despite both excellent neuro surgical Inhibitors,Modulators,Libraries strategies and advances in the treatment of systemic mRCC, the course of disease of patients with brain metastases Inhibitors,Modulators,Libraries remains an enormous challenge. These patients are endangered by rapidly progressing extracerebral metas tases rather than progressing brain metastases. Thus, different i. e. more complex therapeutic concepts are urgently required for this patient population and base Inhibitors,Modulators,Libraries line and repeated CT scans of the brain should be pro vided in all patients in order to enable highly potent local treatment options.

Declaration of competing interests Inhibitors,Modulators,Libraries Manuela Schmidinger has acted as an adviser to Pfizer, Bayer Schering, Wyeth, Novartis, Roche and GSK, has received research grants from Pfizer and Wyeth, travel grants from Bayer Schering and Wyeth and lecture fees from Pfizer, Bayer Schering, Novartis, Roche and Nutlin-3a CAS Wyeth. Christoph Zielinski has acted as an adviser to Pfizer and Roche, has received lecture fees from Pfizer, Merck, Lilly and Roche and research grants from Pfizer and Wyeth. Gero Kramer has received research grants from Sanofi Aventis, Bayer Schering and Takeda, lecture fees from Sanofi Aventis, Astra Zeneca and Astellas, acted as an advisor to Sanofi Aventis and received travel grants from Pfizer, Boehringer Ingelheim, Sanofi Aventis and Bayer Schering. Ursula Vogl has received travel grants from Pfizer, Wyeth Roche and Bayer Schering. Wolfgang Lamm has received travel grants from Bayer Schering. Oskar Pichelmayer has received research grants from Roche and travel grants from Bayer Scher ing. Marija Bojic, Andrea Haitel, Josa Frischer, Kaan Harmankaya and Klaus Kitz have no conflicts of interest to declare.