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<Emphasis Type="Italic">BIM</Emphasis> Deletion Polymorphism Confers Resistance to Osimertinib in <Emphasis Type="Italic">EGFR</Emphasis> T790M Lung Cancer: a Case Report and Literature Review
Authors:Xuanzong Li  Shijiang Wang  Butuo Li  Zhen Wang  Shuheng Shang  Yang Shao  Xindong Sun  Linlin Wang
Institution:1.School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Jinan,China;2.Department of Radiation Oncology,Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science,Jinan,People’s Republic of China;3.Tianjin Medical University,Tianjin,China;4.Department of Oncology,Zhangqiu People’s Hospital,Jinan,China;5.Medical College of Shandong University,Jinan,China;6.Geneseeq Technology Inc.,Toronto,Canada;7.School of Public Health,Nanjing Medical University,Nanjing,China
Abstract:The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against the EGFR T790M mutation in non-small cell lung cancer (NSCLC) patients. However, resistance inevitably occurs, and the mechanisms leading to treatment failure need to be further investigated. The B-cell lymphoma 2 (BCL-2)-like 11 (BIM) deletion polymorphism, which occurs at a frequency of 21% in East Asians but is absent in African and European populations, has been associated with resistance to first-generation EGFR TKIs, such as gefitinib and erlotinib; and is a poor prognostic factor for NSCLC patients with EGFR mutations. Nevertheless, the significance of this BIM deletion polymorphism in the resistance to osimertinib has not been reported. Here, we show for the first time that a NSCLC patient harboring the EGFR L858R/T790M mutations, as well as the BIM deletion polymorphism, exhibited poor clinical outcomes with osimertinib treatment. This result suggests that the BIM deletion polymorphism might have prognostic value for determining NSCLC patient outcomes following osimertinib treatment.
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