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- Title
Mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean patients with lung cancer.
- Authors
Wonjun Ji; Chang-Min Choi; Jin Kyung Rho; Se Jin Jang; Young Soo Park; Sung-Min Chun; Woo Sung Kim; Jung-Shin Lee; Sang-We Kim; Dae Ho Lee; Jae Cheol Lee; Ji, Wonjun; Choi, Chang-Min; Rho, Jin Kyung; Jang, Se Jin; Park, Young Soo; Chun, Sung-Min; Kim, Woo Sung; Lee, Jung-Shin; Kim, Sang-We
- Abstract
<bold>Background: </bold>Despite an initial good response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), resistance to treatment eventually develops. Although several resistance mechanisms have been discovered, little data exist regarding Asian patient populations.<bold>Methods: </bold>Among patients at a tertiary referral hospital in Korea who initially responded well to gefitinib and later acquired resistance to treatment, we selected those with enough tissues obtained before EGFR-TKI treatment and after the onset of resistance to examine mutations by mass spectrometric genotyping technology (Asan-Panel), MET amplification by fluorescence in situ hybridization (FISH), and analysis of AXL status, epithelial-to-mesenchymal transition (EMT) and neuroendocrine markers by immunohistochemistry.<bold>Results: </bold>Twenty-six patients were enrolled, all of whom were diagnosed with adenocarcinoma with EGFR mutations (19del: 16, L858R: 10) except one (squamous cell carcinoma with 19del). Secondary T790M mutation was detected in 11 subjects (42.3%) and four of these patients had other co-existing resistance mechanisms; increased AXL expression was observed in 5/26 patients (19.2%), MET gene amplification was noted in 3/26 (11.5%), and one patient acquired a mutation in the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) gene. None of the patients exhibited EMT; however, increased CD56 expression suggesting neuroendocrine differentiation was observed in two patients. Interestingly, conversion from L858R-mutant to wild-type EGFR occurred in one patient. Seven patients (26.9%) did not exhibit any known resistance mechanisms. Patients with a T790M mutation showed a more favorable prognosis.<bold>Conclusion: </bold>The mechanisms and frequency of acquired EGFR-TKI resistance in Koreans are comparable to those observed in Western populations; however, more data regarding the mechanisms that drive EGFR-TKI resistance are necessary.
- Subjects
EPIDERMAL growth factor receptors; PROTEIN-tyrosine kinase inhibitors; LUNG cancer; GENETIC mutation; MASS spectrometry
- Publication
BMC Cancer, 2013, Vol 13, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/1471-2407-13-606