Cancer Res Treat. 2012;44(3):151-156 Review Article pISSN 1598-2998, eISSN 2005-9256 http://dx.doi.org/10.4143/crt.2012.44.3.151 Open Access Epithelial Mesenchymal Transition in Drug Resistance and Metastasis of Lung Cancer Fariz Nurwidya, MD Fumiyuki Takahashi, MD, PhD Akiko Murakami, MD Kazuhisa Takahashi, MD, PhD Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan + + + + + + + + + + + + + + + + + + + + + C+or+res+po+ndenc+e:+Fa+riz+N+urw+id+ya+,M+D+ + + + + + + D+ep+art+me+nt+of+Re+sp+ira+tor+y M+e+dic+in+e, + + + + + + + + + + + + + + + + + + + + + + + + + + J+un+ten+do+Un+iv+ers+ity+Sc+ho+ol+of+M+ed+icin+e,+ + + + + 2+-1-+1 H+o+ng+o, B+u+nk+yo-+ku+, T+ok+yo+11+3-8+42+1,+Ja+pan+ + T+el:+81+-8+0-3+69+0-+252+9+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + F+ax+:8+1-3+-5+80+2-1+61+7 + + + + + + + + + + + + E+-m+ail+: f+ariz+@+ju+nte+nd+o.a+c.j+p + + + + + + + + + + + + + + + + + + + + + + + + + + + + + R+ec+eiv+ed+M+ar+ch+1,+20+12+ + + + + + + + + + + A+cc+ep+ted+A+pr+il 3+, 2+01+2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + I n t r o d u c t i o n In 2008, lung cancer was reported as the most commonly diagnosed cancer as well as the leading cause of cancer death worldwide in males; among females, it was the fourth most commonly diagnosed cancer and the second leading cause of cancer death [1]. When treated with the most active combination of conventional chemotherapeutic agents, the median period of survival for patients with metastatic non-small cell lung cancer (NSCLC) is eight to 10 months [2]. Failure of treatment is attributed to metastasis and recurrence [3]. Some patients exhibit intrinsic resistance to chemotherapy, while other patients, although initially sensitive to chemotherapy, eventually develop acquired resistance, even after combination therapy. Indeed, metastasis and therapeutic resistance have been reported as the major causes of failure of cancer treatment [3]. To circumvent this situation, a new class of drugs http://www.cancerresearchandtreatment.org http://www.e-crt.org Among all types of cancer, incidence of lung cancer remains the highest with regard to cancer- related mortality. Problems contributing to recurrence of the disease include metastasis and drug resistance. Mounting evidence has demonstrated involvement of epithelial mesenchymal tran- sition (EMT) in cancer progression. EMT is a critical mechanism ensuring tissue remodeling during morphogenesis of multicellular organisms. Therefore, understanding of the biology of this process for identification of potential EMT-targeted therapeutic strategies for the benefit cancer patients is necessary. This review describes recent evidence of EMT involvement in drug resistance and metastasis of cancers, with an emphasis on lung cancer. Key words Epithelial-mesenchymal transition, Drug resistance, Neoplasm metastasis, Lung neoplasms that specifically target certain molecular pathways leading to cancer phenotypes is under development [4]. Small molecules that specifically inhibit the tyrosine kinase (tyrosine kinase inhibitors [TKI]) activity of epidermal growth factor receptor (EGFR), such as gefitinib and erlotinib, were the first drugs to become clinically available for treatment of patients with NSCLC [4]. However, despite the efficacy of these drugs in patients with activating mutations, development of acquired resistance in these targeted therapies seems inevitable [5]. Results of multiple prospective trials have shown a response rate of 70% to 75% to TKIs for patients with tumors harboring EGFR mutations [6]. However, this finding indicates that another 25% to 30% of patients have intrinsic resistance to EGFR- TKIs, even though their tumors harbor activating mutations in EGFR. In addition, almost without exception, even patients who show a dramatic response to initial treatment also develop acquired resistance to EGFR- TKI after varying periods of time [7]. Failure of treatment may lead to metastasis of lung cancer. Among organ targets, brain metastasis is a Copyright 2012 by the Korean Cancer Association 151 This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/3.0/)which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.