The suitability of PA 824 in replacing standard anti tubercular drugs in the ini

Endothelial cells in parental and nontargeting shRNA tumors expressed phosphorylated EGFR. Therapy with PKI166 alone or with irinotecan produced apoptosis of these endothelial Tipifarnib cells and necrosis of the EGFR negative tumors. Endothelial cells in tumors that did not express TGF did not express EGFR, and these tumors were resistant to treatment with PKI166. The response of neoplasms to EGFR antagonists has been correlated with EGFR mutations, HER2 expression, Akt activation, and EGFR gene copy number. Our present data using colon cancer cells that do not express EGFR or HER2 suggest that the expression of TGF by tumor cells leading to the activation of EGFR in tumor associated endothelial cells is a major determinant for the susceptibility of neoplasms to therapy by specific EGFR TKI. The major cause of death from cancer is due to metastases that are resistant to conventional therapies. The genetic instability of tumor cells in general and metastatic cells in particular is responsible for generating biologic heterogeneity in metastatic Endosymbiotic theory lesions which is a major cause for the failure of systemic antitumor therapy. Because the progressive growth and survival of all neoplasms are dependent on the development of an adequate vascular supply, targeting the tumor vasculature can be an effective approach for therapy for primary tumors in general and metastases in particular. Growth factors and their receptors play a central role in the progressive growth of neoplasms. Overexpression of the epidermal growth factor receptor and its ligands, transforming growth Abbreviations: Gemcitabine EGF, epidermal growth factor, EGFR, EGF receptor, HER2, human epidermal growth factor receptor 2, PKI166, 4 phenethylamino 6 phenyl 7H pyrrolo pyrimidine, shRNA, small hairpin RNA, TGF, transforming growth factor, TKI, tyrosine kinase inhibitor factor /EGF by many cancers has been correlated with poor prognosis. Colon cancer cells secrete TGF in response to hypoxia and the ligand signals, the cell surface EGFR, to initiate a sequence of cell survival programs. This activation of the EGFR signaling pathways contributes to cell proliferation and survival by triggering downstream signaling molecules, such as Akt and mitogen activated protein kinase. The close association between coexpression of TGF /EGF and EGFR in tumor cells and stroma cells with resistance to chemotherapy and hence poor survival has advanced EGFR as a logical target for therapy. Small molecule EGFR tyrosine kinase inhibitors have been studied in multiple clinical trials against relapsed non?small cell lung cancer. However, only a small percentage of the patients responded to EGFR antagonists given as a single agent. Whether the sensitivity to EGFR TKI is correlated to the expression level of EGFR on tumor cells has been controversial.