The role of the epidermal growth factor receptor (EGFR)/Posphorylated-Akt (P-Akt) signaling axis in regulating hypoxia-inducible factor-1alpha (HIF-1alpha) expression in vivo is not well understood and is of potential clinical importance since the extent of hypoxia in the tumor environment is thought to be an important determination of resistance to chemotherapy and radiotherapy. We performed the immunohistochemical studies in 80 patients with non-small cell lung cancers to evaluate EGFR, P-Akt, and HIF-1alpha expression. Significant correlation between P-Akt and HIF-1alpha (P=0.0006) and marginal correlation between EGFR and P-Akt (P=0.066) were found. P-Akt was shown to be a poor prognostic factor as to patients with lymph node involvement (P=0.031).

Background: YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC).

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