Growth factor receptors are overexpressed in most cancers and their presence correlates with poor prognosis. Activation of EGF- and IGF-signaling pathways results in increased proliferation, motility and resistance to chemo- and radiation therapy. It has been shown that the resistance of tumor cells to targeted therapy based on blocking individual growth factor signaling pathways may be caused by cross-talk with another growth factor pathway. For example, activation of IGFR pathway interferes with anti-EGF pathway therapy. In order to increase tumor sensitivity to radiation, we will investigate a multi-target approach blocking both EGF and IGF pathways by:1) In silico, in vitro and in vivo studies of the effects of simultaneous blockage of various steps of EGF and IGF signaling pathways on tumor and normal tissues.2) Study of the effects of blocking of the relevant pathways bon the outcome of radiotherapy in order to identify optimal combination for clinical trials.3) In vivo visualization of the signaling components to monitor the effects of therapy on their activities.
| Koll, Thuy T; Feis, Steven S; Wright, Mollie H et al. (2008) HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair. Mol Cancer Ther 7:1985-92 |
