Or other anomalies phosphatidylinositol 3-kinase and cancer driven by KRAS not be sensitive, although in some F Cases, there is evidence that the synergy in the KRAS mutation can be achieved by the combination of phosphatidylinositol 3 kinase and MEK 1/2- inhibitors. Because this article describes the most important aspects of a program of drug discovery, cell Trichostatin A TSA lines and xenograft models used are weight hlt Because they had deliberately deregulated phosphatidylinositol 3-kinase signaling found also mechanisms in human tumors in the clinic. However, k can The first tentative interpretations of the effects of certain oncogenic abnormalities in the distribution of responses to be made to the class of drugs thienopyrimidines studied here by the panel of cancer cell lines studied so far.
First, it is clear that differences in in-vitro susceptibility to these agents among different cancer cell lines examined here may be due to differences in Ausma the inhibition of phosphatidylinositol 3-kinase, because it has been shown remarkable similar, with IC 50 values for inhibition of phosphorylation of Ser473 the varying only about 2 to 3 times in the control line of cancer cells with respect to a very much larger ere differences in the values of GI50 antiproliferative response. This document clearly shows a differential proliferative response to a given degree of blockade of phosphatidylinositol 3-kinase, indicating the involvement of other factors. It is interesting to note that, as before with PI 103, IC50 values observed quantitative phosphatidylinositol 3-kinase pathway inhibition is much lower than the values of the GI50 for the anti-proliferative response.
This suggests that ben the 50% inhibition of the channel To do prior to stop the growth of cancer cells by 50%. Second, the analysis indicates the sensitivity to antiproliferative PIK3CA, PTEN, and KRAS status, that there is no obvious simple picture that is studied for the class of inhibitors of phosphatidylinositol 3 thienopyrimidines date kinases. For example, in the small group of three human cancer cell lines of the large intestine in this paper Examined ffentlichung,, the line represents a lower LoVo GI50 at GDC 0941, that HCT116 having a GI50 of 905 nmol / l, although a SNUC2CB most of GI50 1627 nmol / L. Note also that there is an overlap in sensitivity between the three tumor cell lines of c Lon, who was all mutants KRAS and other cancer cell lines examined here.
4 Interestingly, in an independent Was ngigen study on a panel of cancer cell lines, there is still no motive for the in vitro susceptibility at GDC 0941 to the mutation status of genes such as PIK3CA, PTEN, and KRAS, and among other things, that human tumor xenografts responded to the GDC 0941 was a non-small cell lung cancer with mutated KRAS. Closing Lich should be noted that non-malignant cells, umbilical vein endothelial cells here are very sensitive to 3-phosphatidylinositol kinase inhibitors, which are displayed on a dependence Dependence of the phosphatidylinositol 3-kinase activity t. It is therefore likely that the in vivo response that is seen in an animal tumor model adversely by a component of the anti-angiogenic inhibition of phosphatidylinositol 3-kinase Chtigt may be, as we mentioned earlier HNT for IP 103rd Look before