Open Access
Kinase-driven pathways of EGFR in lung carcinomas: perspectives on targeting therapy
Yoh Dobashi1,Shinichiro Koyama1,Yoshihiko Kanai1,Kenji Tetsuka1
Department of Pathology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
DOI: 10.2741/3815 Volume 16 Issue 5, pp.1714-1732
Published: 01 January 2011

Despite remarkable advances in oncology medicine, the prognosis of lung cancer patients has not greatly improved over the past few decades. To overcome the current limit, new classes of agents that specifically target particular cascades have been developed. Gefitinib and erlotinib, which are tyrosine kinase inhibitors specific for the epidermal growth factor receptor (EGFR), have provided hope for better survival. The relationship between the sensitivity to gefitinib and the tumors' EGFR mutations have allowed the selective and accelerated use of these therapies. However, their efficacy is still limited, predominantly due to side effects and drug resistance. Further development of rational clinical strategies will require greater clarification of the key signaling factors downstream of EGFR which are potential targets for cancer therapies. In this review, we describe the various observed abnormalities in EGFR, the mechanisms of activation of several critical signaling cascades in lung cancer. Summarizing the data gleaned from preclinical, and clinicopathological aspects, we discuss the molecular mechanisms that may underlie a possible successful response to the blockade of EGFR and/or its downstream signaling.

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Yoh Dobashi, Shinichiro Koyama, Yoshihiko Kanai, Kenji Tetsuka. Kinase-driven pathways of EGFR in lung carcinomas: perspectives on targeting therapy. Frontiers in Bioscience-Landmark. 2011. 16(5); 1714-1732.