13 March 2013 Photonic cancer therapy: modulating cellular metabolism with light
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Abstract
The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases. EGFR activation upon binding of ligands (such as EGF and TGF-α) results in cell signaling cascades that promote cell proliferation, survival and apoptosis inhibition. As reported for many solid tumors, EGFR overactivation is associated with tumor development and progression, resistance to cancer therapies and poor prognosis. Therefore, inhibition of EGFR function is a rational cancer therapy approach. We have shown previously that 280 nm UV illumination of two cancer cell lines overexpressing EGFR could prevent phosphorylation of EGFR and of its downstream signalling molecules despite the presence of EGF. Our earlier studies demonstrated that UV illumination of aromatic residues in proteins leads to the disruption of nearby disulphide bridges. Since human EGFR is rich in disulphide bridges and aromatic residues, it is likely that structural changes can be induced upon UV excitation of its pool of aromatic residues (Trp, Tyr and Phe). Such changes may impair the correct binding of ligands to EGFR which will halt the process of tumor growth. In this paper we report structural changes induced by UV light on the extracellular domain of human EGFR. Steady state fluorescence spectroscopy and binding immunoassays were carried out. Our goal is to gain insight at the protein structure level that explains the way the new photonic cancer therapy works. This technology can be applicable to the treatment of various forms of cancer, alone or in combination with other therapies to improve treatment outcome.
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Isabel Coutinho, Isabel Coutinho, Manuel Correia, Manuel Correia, Thiagarajan Viruthachalam, Thiagarajan Viruthachalam, Gnana Prakash Gajula, Gnana Prakash Gajula, Steffen B Petersen, Steffen B Petersen, Maria Teresa Neves-Petersen, Maria Teresa Neves-Petersen, "Photonic cancer therapy: modulating cellular metabolism with light", Proc. SPIE 8568, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXII, 856806 (13 March 2013); doi: 10.1117/12.2004043; https://doi.org/10.1117/12.2004043
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