This underscores the need for novel agents with improved efficacy and safety profiles. Among those, the epidermal growth factor receptor is one of the most important targets in NSCLC therapy. The currently available agents targeting EGFR in NSCLC this treatment are two small molecular tyrosine kinase inhi bitors, including gefitinib and erlotinib. A phase III, open label study demonstrated the presence in the tumor of a mutation of the EGFR Inhibitors,Modulators,Libraries gene is a strong pre dictor of a better outcome with gefitinib. Even more, EGFR TKI was recently recommended to be the first line therapy in EGFR mutation positive patients with NSCLC. Unfortunately, the responsive rate to the EGFR TKIs is low for reasons such as primary or secondary resistance.

Thus, no adequate treatment options currently exist for EGFR tumor driven patients who have experi enced EGFR TKIs and chemotherapy failure. In recent years, RNA Inhibitors,Modulators,Libraries interference has drawn attention in therapeutic studies of cancer. It was discovered to be a process of post transcriptional gene silencing, which induces degradation of a homologous messenger RNA and protein knock down in a sequence specific manner. Due to this property, siRNA sequences have been designed for many target mRNAs. For example, the target of interest could be a mutated protein, as in the case of NSCLC patients resist ant to EGFR TKIs. Additionally, conventional small molecule drug discovery involves complicated screening and random modifications, thus leading to new com pounds. However, to design a therapeutic siRNA requires only knowledge of the target genes sequence, and thus can be chemically synthesized at relatively low cost.

In this regard, the novel therapeutic modality of siRNA based gene silencing may have advantages Inhibitors,Modulators,Libraries over drugs currently on the market. However, for further in vivo application, the negative charge and chemical degradability of siRNA under physio logically relevant conditions make its delivery a major challenge. Viral vectors have high in vitro gene transfer efficiency, but their limited carrying ability of genetic material and severe safety risks induced by their immuno genicity and oncogenic potentials deter broad use in Inhibitors,Modulators,Libraries humans. Recently, non viral vectors have been inves tigated for their ease of preparation, purification, and chemical modification, as well as their stability. Among these lipoplexes have shown significant toxicities.

In con trast, the cationic polymers, polyethylenimine, are regarded as the most efficient and versatile non viral Inhibitors,Modulators,Libraries vec tors. Of these, linear PEI has been widely employed in click this gene transfer into varied organs, such as lung, brain, retina, pancreas, and bladder tumors. Clinical trials for the treatment of bladder cancer and human immunodeficiency virus infection have been underway, using LPEI mediated plasmid DNA delivery. Moreover, this delivery system has recently been suc cessfully applied in siRNA delivery in vivo.