Components such as smoking Wnt Pathway butanone-4 1 1 has been shown that genetic Ver Changes in p53 and PTEN, which the IGF-2 and IGF 1R expression.33, 34 NNK also induces the phosphorylation and degradation of p53 on regulation to induce activation of update 35 Even if we have no evidence for smoking mechanical activation of IGF signaling 1R/IR induced carcinogenesis in the lungs, the effects of IGF-1R way to survive in cell proliferation and have suggested targeting that IGF 1R nnte k an effective therapeutic strategy for patients with NSCLC with his tobacco smoking history. This term, and our sp Teren findings confinement Usually choose Properties patients with NSCLC a high Ma were negatively correlated with those of PlGF 1R/IR of patients with EGFR mutation, and the treatment effectively inhibited ICQN stimulation of the path of IGF 1R, but had little antitumor activity t in NSCLC cells expressing mutant EGFR, led us to the hypothesis that pr is a history of smoking and mutation of the EGFR predictive biomarkers is the lack of response to IGF 1R ITC. However, we found that only a part of human NSCLC cell lines sensitive and PlGF with high 1R/IR WT EGFR were ICQN to treatment. These observations suggest that EGFR mutation is not a pr Diktiver marker of response to IGF 1R TKI-based therapies. Since the m Possible mechanisms of crosstalk between EGFR and IGF-1R signaling 18.36, 38 inhibition of IGF 1R signaling can be obtained by the Hte compensated by the activation of EGFR. However, no NSCLC cells expressing mutant Ras not reduced significantly improved sensitivity w in response to cotargeting of IGF 1R and EGFR by treatment with EGFR TKI ICQN and erlotinib, During the same pattern clearly the Lebensf Ability of the cells into a subset of head and carcinoma Epidemo Cell lines, the K-ras WT. It has been suggested that the sensitivity of NSCLC cells to TKIs of the IGF 1R and EGFR, either alone or combination thereof, by the epithelial cells to mesenchymal transition.36 is determined 39, however, was not the transient time epithelial mesenchymal state, a pr Diktiver marker for a consistent insensitivity to antagonism against IGF 1R and IGF 1R and cotargeting EGFR.36 These results demonstrate the involvement of additional keeping biomolecules, the cellular re response to IGF 1R differentiate NSCLC ITC. Our current results from several in vitro and in vivo that mutant K-Ras, the response to IGF-1R inhibitors is different. In the present study, we found that detection pathway activation of IGF 1R with K ras mutations, which increase production of IGF-1 increased Hen k Can correlate how much h Heres demonstrated high IGF-1 in the conditioned media of cells expressing mutant K H226B Ras compared to those harboring WT K ras. Therefore, k Be nnte K ras mutation is a driving force for pathway activation of IGF 1R and can be a pr Diktiver markers of sensitivity to IGF 1R blockade be. However, our subsequent results clearly show that mutant Ras, K is a pr diktiver marker for poor therapeutic efficacy: a K Ras mutant leads to an increased Hten resistance in many test systems ICQN, and 2 of the inactivation of K Ras or MEK by pharmacological or genomic Ans is COLUMNS similar to the anti-tumor activity t of IGF 1R TKI in vitro and in vivo in mutants induced.