Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers
Hisayuki Shigematsu,Hisayuki Shigematsu,Li Lin,Takao Takahashi,Masaharu Nomura,Makoto Suzuki,Ignacio I. Wistuba,Kwun M. Fong,Huei Lee,Shinichi Toyooka,Nobuyoshi Shimizu,Takehiko Fujisawa,Ziding Feng,Jack A. Roth,Joachim Herz,John D. Minna,Adi F. Gazdar +16 more
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TLDR
EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers, and can lead to lung cancer pathogenesis.Abstract:
Background: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. Methods: We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. Results: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P <.001). EGFR TK domain mutation status was not associated with patient age at diagnosis, clinical stage, the presence of bronchioloalveolar histologic features, or overall survival. The EGFR TK domain mutations we detected were of three common types: in-frame deletions in exon 19, single missense mutations in exon 21, and in-frame duplications/insertions in exon 20. Rare missense mutations were also detected in exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617 NSCLCs but not in any tumors with an EGFR TK domain mutation. Conclusions: Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers.read more
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Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Tony Mok,Yi-Long Wu,Sumitra Thongprasert,Chih-Hsin Yang,Da Tong Chu,Nagahiro Saijo,Patrapim Sunpaweravong,Baohui Han,Benjamin Margono,Benjamin Margono,Yukito Ichinose,Yutaka Nishiwaki,Yuichiro Ohe,Jin Ji Yang,Busyamas Chewaskulyong,Haiyi Jiang,Emma Duffield,Claire Watkins,Alison Armour,Masahiro Fukuoka +19 more
TL;DR: Gefit inib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia and the presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib.
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International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma
William D. Travis,Elisabeth Brambilla,Masayuki Noguchi,Andrew G. Nicholson,Kim R. Geisinger,Yasushi Yatabe,David G. Beer,Charles A. Powell,Gregory J. Riely,Paul Van Schil,Kavita Garg,John H. M. Austin,Hisao Asamura,Valerie W. Rusch,Fred R. Hirsch,Giorgio V. Scagliotti,Tetsuya Mitsudomi,Rudolf M. Huber,Yuichi Ishikawa,James R. Jett,Montserrat Sanchez-Cespedes,Jean-Paul Sculier,Takashi Takahashi,Masahiro Tsuboi,Johan Vansteenkiste,Ignacio I. Wistuba,Pan-Chyr Yang,Denise R. Aberle,Christian Brambilla,Douglas B. Flieder,Wilbur A. Franklin,Adi F. Gazdar,Michael K. Gould,Philip S. Hasleton,Douglas W. Henderson,Bruce E. Johnson,David A Johnson,Keith M. Kerr,Keiko Kuriyama,Jin Soo Lee,Vincent A. Miller,Iver Petersen,Victor L. Roggli,Rafael Rosell,Nagahiro Saijo,Erik Thunnissen,M. Tsao,David Yankelewitz +47 more
TL;DR: This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies.
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Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
Caicun Zhou,Yi-Long Wu,Gongyan Chen,Jifeng Feng,Xiaoqing Liu,Changli Wang,Shucai Zhang,Jie Wang,Songwen Zhou,Shengxiang Ren,Shun Lu,Li Zhang,Chengping Hu,Chunhong Hu,Yi Luo,Lei Chen,Ming Ye,Jian'An Huang,Xiuyi Zhi,Yiping Zhang,Qingyu Xiu,Jun Ma,Changxuan You +22 more
TL;DR: It is suggested that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC, and was associated with more favourable tolerability than standard chemotherapy.
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Epidermal growth factor receptor mutations in lung cancer
TL;DR: 'oncogenic shock' is described as a mechanistic explanation for the apoptosis that follows the acute treatment of susceptible cells with kinase inhibitors, essential to the successful use of targeted therapies in common epithelial cancers.
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Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)
Nick Thatcher,Alex R. Chang,Purvish M. Parikh,José Rodrigues Pereira,Tudor Ciuleanu,Joachim von Pawel,Sumitra Thongprasert,Eng Huat Tan,Kristine Pemberton,Venice Archer,Kevin H Carroll +10 more
TL;DR: Treatment with gefitinib was not associated with significant improvement in survival in either coprimary population, and there was pronounced heterogeneity in survival outcomes between groups of patients, with some evidence of benefit among never-smokers and patients of Asian origin.
References
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TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.
Journal ArticleDOI
Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
Joan H. Schiller,David P. Harrington,Chandra P. Belani,Corey J. Langer,Alan B. Sandler,James E. Krook,Junming Zhu,David H. Johnson +7 more
TL;DR: None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer.
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Revisions in the International System for Staging Lung Cancer
TL;DR: Analysis of a collected database representing all clinical, surgical-pathologic, and follow-up information for 5,319 patients treated for primary lung cancer confirmed the validity of the TNM and stage grouping classification schema.
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