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Advanced Non-Small Cell Lung Carcinoma: Acquired Resistance to Gefitinib

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General Methods and Overviews, Lung Carcinoma and Prostate Carcinoma

Part of the book series: Methods of Cancer Diagnosis, Therapy, and Prognosis ((HAYAT,volume 2))

Epidermal growth factor receptor (EGFR) signaling regulates processes essential to tumor progression, including cell motility, cell adhesion, tumor invasion, cell survival, and angiogenesis as well as cell proliferation (Mendelsohn, 2000). Since EGFR is expressed in ~50% of non-small cell lung cancer (NSCLC) tumors (Veale et al., 1987), this receptor is a candidate for targeted therapeutics in the treatment of NSCLC. Gefitinib (Iressa: AstraZeneca) is a novel, low-molecular-weight synthetic anilinoquinazoline [4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)-quinazoline] (Ward et al., 1994). Its discovery was based on studies designed to characterize the mechanism of catalysis of EGFR tyrosine kinase (TK) inhibition. During the initial phase of the development of gefitinib, researchers aimed at disease control or long-term disease stability. Unexpectedly, however, they experienced a dramatic response to gefitinib in a patient with advanced NSCLC (Fukuoka et al., 2003; Fujiwara et al., 2003). The marked response observed in this patient, which had never been seen previously in patients with advanced NSCLC impressed physicians who had treated incurable, advanced NSCLC in Japan. Similar dramatic responses to gefitinib were observed in a small but substantial subset of NSCLC patients including those of female gender with adenocarcinoma histology (Fukuoka et al., 2003; Kris et al., 2003). These patients were nonsmokers and of East Asian ethnicity (Fukuoka et al., 2003; Miller et al., 2004). However, although gefitinib was employed throughout the world, the mechanisms responsible for its efficacy had remained unclear.

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Authors and Affiliations

  1. DePartment of Respiratory Medicine, Okayama University Hospital, Graduate School of Medicine, Okayama, 700-8558, Japan

    Katsuyuki Kiura & Nagio Takigawa

  2. DePartment of Medicine and Thoracic Oncology, National Hospital Organization, Shikoku Cancer Center, 160 Kou-Minami-Umemoto-cho, Matsuyama, Ehime, 791-0288, Japan

    Yoshihiko Segawa

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  1. Katsuyuki Kiura
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  2. Nagio Takigawa
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  3. Yoshihiko Segawa
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Correspondence to Nagio Takigawa or Yoshihiko Segawa .

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  1. Department of Biological Sciences, Kean University, Union, NJ, USA

    M. A. Hayat

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Kiura, K., Takigawa, N., Segawa, Y. (2008). Advanced Non-Small Cell Lung Carcinoma: Acquired Resistance to Gefitinib. In: Hayat, M.A. (eds) General Methods and Overviews, Lung Carcinoma and Prostate Carcinoma. Methods of Cancer Diagnosis, Therapy, and Prognosis, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8442-3_21

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