This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.(from CRISP website)Cancer is one of the areas of human health where technological breakthroughs have resulted in major advances in understanding the molecular basis of disease. Knowledge concerning the role of key signaling proteins in cancer has prompted attempts to develop anti-cancer agents directed against signaling targets such as the epidermal growth factor receptor (EGFR). However, little information is available regarding the precise mechanisms of action of these anti-cancer agents in human tumors, primarily due to the difficulty in performing relevant molecular assays on limited tissue material. This lack of understanding regarding how these agents affect EGFR-mediated events in human tumors has made clinical investigation into this area extremely difficult. This multi-disciplinary team of researchers from the Medical School and the College of Engineering are presently working together to establish an integrated approach, which revolves around the development and utilization of a fundamentally new class of exquisitely sensitive tools that exploit recent advances in nano-scale materials science for molecular analysis. The information derived from minimal amounts of clinical specimens using this new method of analysis will enable physicians to determine which regulatory protein pathways are most likely to respond to EGFR tyrosine kinase inhibitors. The creation and use of these new tools involves (1) the fabrication of nano-structured surfaces, (2) employing the orientational behavior of liquid crystals (LCs) as a powerfully precise means of road-out of specific binding events to receptors decorated on the nanostructured surfaces, and (3) validating these techniques in tumor samples from lung cancer patients receiving EGFR inhibitors. To accomplish these goals, the following specific aims were proposed: 1) Develop a new methodology using LCs and nano-structured surfaces for evaluation of the expression and extent of activation of EGFR on limited clinical specimens; and 2) Validate the molecular analysis tools developed in Aim 1 by identifying in-vivo alterations in the EGFR pathway, following administration of tyrosine kinase-dirocted anticancer drugs in tumor samples from cancer patients receiving EGFR inhibitors.
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