Conclusions These preclinical studies indicate that the pharmacoki netic and pharmacodynamic selleck products parameters of panitumu mab correlated with in vivo antitumor activity. Furthermore, understanding these parameters may help to understand the responses seen in patients receiving panitumumab treatment. Introduction Despite significant therapeutic advances, lung cancer causes the maximum number of cancer related deaths worldwide. In the United States, 85% of the patients diagnosed with NSCLCs, die within five years, thus, highlight a need for better understanding of the cellular and molecular events underlying the genesis of this dis ease. Cancer stem cell model has emerged as a viable explanation for the initiation and progression of the ag gressive cancers like NSCLCs.

Cancer stem cell model suggests that cancer stem like cells are a subpopulation of cells within the Inhibitors,Modulators,Libraries tumor that have the Inhibitors,Modulators,Libraries deregulated properties of normal stem cells with sustained self renewal, and can generate secondary tumors that recapitulate the heterogeneity and diversity of original tumor. CSCs are consid ered to be responsible for tumor initiation, propagation, recurrence and resistance to therapy. Hoechst 33342 dye excluding cells, termed side population cells, have been described as CSCs in a variety of tumor types, including NSCLCs, Inhibitors,Modulators,Libraries where they have been shown to display increased tumorigenicity when trans planted into immunocompromised mice as com pared to major population Inhibitors,Modulators,Libraries cells.

SP phenotype is dependent on the differential ability of cells to efflux the Hoechst 33342 dye via the ATP binding cassette family of transporter protein, mainly ABCG2 which is specifically expressed on the cell membrane of stem cell populations. Earlier studies have demonstrated the existence of SP cells Inhibitors,Modulators,Libraries in various established human NSCLC cell lines but their ability to generate tumors in lung micro environment as well as the signaling pathways governing their stem like properties remain to be elucidated. The transcription factors Oct4, Sox2 and Nanog have been identified as core regulators that maintain the self renewal of embryonic stem cells. These factors are overexpressed in various cancers and are associated with malignant progression and poor prognosis including NSCLCs, suggesting that the core regulators that govern normal stem cell self renewal may also maintain the stem like properties of CSCs in cancers.

However, the influence of NSCLC specific oncogenic pathways on the expression of these factors remains relatively un known. Alterations in EGFR gene like copy number gains and or mutant allele specific amplifications are associated with NSCLC pathogenesis. In addition, selleck MEK162 activa tion of EGFR signaling increases the self renewal cap acity of neural precursor cells and brain tumor stem cells.