In other systems, the normally targeting of platelets or experimental decrease in their numbers has been shown to enhance cancer chemother apy. Platelets are the source of multiple growth factors, cyto kines and inflammatory mediators. Included among them are EGF, IGF I, fibroblast growth factor, platelet derived growth factor and serotonin, Inhibitors,Modulators,Libraries the modulation of each having been shown Inhibitors,Modulators,Libraries to alter cancer chemotherapy sensitivity or resistance. Preliminary data, obtained with several growth factors included in hPL, revealed interesting results using EGF and IGF I. Both these factors were able to antagonized Sorafenib in a proliferation assay, in par ticular when used in combination. This growth induc tion was more evident than that observed in absence of drug, suggesting a specific interference of these growth factors with the inhibitory action of Sorafenib.

Interestingly, the clinical insulin modulator and dia betes drug, metformin and the serotonin modulator Fluoxetine Prozac that is used in depression treatment, each alter chemotherapy sensitivity in cancer cells. Multiple pathways have been found to be involved in Sorafenib mediated growth inhibition, especially Inhibitors,Modulators,Libraries apoptosis and autophagy as well as others and several cytokines, or cytokine modulators that are pro duced by platelets can modulate Sorafenib activity. Since Sorafenib effects have been clinically modest, several approaches are under way to enhance its actions, either on its downstream targets, or by adding inhibitors of parallel pathways in combination therapies.

Given the large number of candidate factors in platelets, the identification of those responsible for drug resistance is just beginning. Inhibitors,Modulators,Libraries However, FGF, IGF1 and serotonin would seem to be promising possibilities. The recent finding that platelet inhibitors reduce hepa titis B associated experimental HCC has led to new interest in the use of aspirin and other platelet inhibitors Inhibitors,Modulators,Libraries in HCC prevention, as in colon cancer prevention. Thrombocytosis has been shown to be a negative prog nostic factor for renal, breast, ovary, pancreas and selleck chem colon cancers. Therefore, the results from this paper might be applicable to those tumor types, especially to renal can cer, since Sorafenib is also FDA approved for treatment of renal cancer. Conclusion The current results give support to the idea that platelet inhibitors might also be useful in the drug therapy of patients with unresectable HCC, provided their platelet levels and coagulation systems are normal. Background Hypoxia in the tumor microenvironment is associated with poor prognosis and a poor response to therapy, underlying the importance of studying the effect of potential anti cancer drugs on the hypoxia pathway.