Sensitivity and kinase activity of epidermal growth factor receptor (EGFR) exon 19 and others to EGFR-tyrosine kinase inhibitors

被引:46
作者
Furuyama, Kazuto [1 ]
Harada, Taishi [1 ]
Iwama, Eiji [1 ]
Shiraishi, Yoshimasa [1 ]
Okamura, Kyoko [1 ]
Ijichi, Kayo [1 ]
Fujii, Akiko [1 ]
Ota, Keiichi [1 ]
Wang, Shuo [1 ]
Li, Heyan [1 ]
Takayama, Koichi [1 ]
Giaccone, Giuseppe [2 ]
Nakanishi, Yoichi [1 ]
机构
[1] Kyushu Univ, Chest Dis Res Inst, Grad Sch Med Sci, Fukuoka 812, Japan
[2] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
关键词
CELL LUNG-CANCER; ACQUIRED-RESISTANCE; PHASE-I; FUNCTIONAL-ANALYSIS; SOMATIC MUTATIONS; GENE-MUTATIONS; GEFITINIB; ERLOTINIB; ADENOCARCINOMA; MODELS;
D O I
10.1111/cas.12125
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The presence of epidermal growth factor receptor (EGFR) somatic mutations in non-small-cell lung cancer patients is associated with response to treatment with EGFR-tyrosine kinase inhibitors, such as gefitinib and erlotinib. More than 100 mutations in the kinase domain of EGFR have been identified. In particular there are many variations of deletion mutations in exon 19. In this study, using yellow fluorescent protein-tagged fragments of the EGFR intracellular domain, we examined the differences in sensitivity to gefitinib, erlotinib and afatinib between several exon 19 mutants and other common EGFR mutations. We also used serum of patients undergoing treatment with EGFR-tyrosine kinase inhibitors in this system. In addition, we examined the relative kinase activity of these mutants by measuring relative fluorescent intensity after immunofluorescence staining. We found that both sensitivity to EGFR-tyrosine kinase inhibitors and relative kinase activity differed among several EGFR mutations found in the same region of the kinase domain. This study underscores the importance of reporting the clinical outcome of treatment in relation to different EGFR mutations.
引用
收藏
页码:584 / 589
页数:6
相关论文
共 30 条
[1]   Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor - Mutant lung adenocarcinomas with acquired resistance to kinase inhibitors [J].
Balak, Marissa N. ;
Gong, Yixuan ;
Riely, Gregory J. ;
Somwar, Romel ;
Li, Allan R. ;
Zakowski, Maureen F. ;
Chiang, Anne ;
Yang, Guangli ;
Ouerfelli, Ouathek ;
Kris, Mark G. ;
Ladanyi, Marc ;
Miller, Vincent A. ;
Pao, William .
CLINICAL CANCER RESEARCH, 2006, 12 (21) :6494-6501
[2]   Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types [J].
Baselga, J ;
Rischin, D ;
Ranson, M ;
Calvert, H ;
Raymond, E ;
Kieback, DG ;
Kaye, SB ;
Gianni, L ;
Harris, A ;
Bjork, T ;
Averbuch, SD ;
Feyereislova, A ;
Swaisland, H ;
Rojo, F ;
Albanell, J .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (21) :4292-4302
[3]   Clinical Outcomes in Non-Small Cell Lung Cancers Harboring Different Exon 19 Deletions in EGFR [J].
Chung, Kuei-Pin ;
Wu, Shang-Gin ;
Wu, Jenn-Yu ;
Yang, James Chih-Hsin ;
Yu, Chong-Jen ;
Wei, Pin-Fei ;
Shih, Jin-Yuan ;
Yang, Pan-Chyr .
CLINICAL CANCER RESEARCH, 2012, 18 (12) :3470-3477
[4]   Functional analysis of cancer-associated EGFR mutants using a cellular assay with YFP-tagged EGFR intracellular domain [J].
de Gunst, Matheus M. ;
Gallegos-Ruiz, Marielle I. ;
Giaccone, Giuseppe ;
Rodriguez, Jose Antonio .
MOLECULAR CANCER, 2007, 6 (1)
[5]   PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib [J].
Engelman, Jeffrey A. ;
Zejnullahu, Kreshnik ;
Gale, Christopher-Michael ;
Lifshits, Eugene ;
Gonzales, Andrea J. ;
Shimamura, Takeshi ;
Zhao, Feng ;
Vincent, Patrick W. ;
Naumov, George N. ;
Bradner, James E. ;
Althaus, Irene W. ;
Gandhi, Leena ;
Shapiro, Geoffrey I. ;
Nelson, James M. ;
Heymach, John V. ;
Meyerson, Matthew ;
Wong, Kwok-Kin ;
Janne, Pasi A. .
CANCER RESEARCH, 2007, 67 (24) :11924-11932
[6]   Characterization of epidermal growth factor receptor mutations in non-small-cell lung cancer patients of African-American ancestry [J].
Harada, T. ;
Lopez-Chavez, A. ;
Xi, L. ;
Raffeld, M. ;
Wang, Y. ;
Giaccone, G. .
ONCOGENE, 2011, 30 (15) :1744-1752
[7]   EGFR Exon 19 Insertions: A New Family of Sensitizing EGFR Mutations in Lung Adenocarcinoma [J].
He, Mai ;
Capelletti, Marzia ;
Nafa, Khedoudja ;
Yun, Cai-Hong ;
Arcila, Maria E. ;
Miller, Vincent A. ;
Ginsberg, Michelle S. ;
Zhao, Binsheng ;
Kris, Mark G. ;
Eck, Michael J. ;
Jaenne, Pasi A. ;
Ladanyi, Marc ;
Oxnard, Geoffrey R. .
CLINICAL CANCER RESEARCH, 2012, 18 (06) :1790-1797
[8]   Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies [J].
Hidalgo, M ;
Siu, LL ;
Nemunaitis, J ;
Rizzo, J ;
Hammond, LA ;
Takimoto, C ;
Eckhardt, SG ;
Tolcher, A ;
Britten, CD ;
Denis, L ;
Ferrante, K ;
Von Hoff, DD ;
Silberman, S ;
Rowinsky, EK .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (13) :3267-3279
[9]   Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib [J].
Jackman, David M. ;
Yeap, Beow Y. ;
Sequist, Lecia V. ;
Lindeman, Neal ;
Holmes, Alison J. ;
Joshi, Victoria A. ;
Bell, Daphne W. ;
Huberman, Mark S. ;
Halmos, Balazs ;
Rabin, Michael S. ;
Haber, Daniel A. ;
Lynch, Thomas J. ;
Meyerson, Matthew ;
Johnson, Bruce E. ;
Jaenne, Pasi A. .
CLINICAL CANCER RESEARCH, 2006, 12 (13) :3908-3914
[10]   The Epidermal Growth Factor Receptor-L861Q Mutation Increases Kinase Activity without Leading to Enhanced Sensitivity Toward Epidermal Growth Factor Receptor Kinase Inhibitors [J].
Kancha, Rama Krishna ;
Peschel, Christian ;
Duyster, Justus .
JOURNAL OF THORACIC ONCOLOGY, 2011, 6 (02) :387-392