BIM Deletion Polymorphism Confers Resistance to Osimertinib in EGFR T790M Lung Cancer: a Case Report and Literature Review

AbstractThe third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against theEGFR 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 withEGFR mutations. Nevertheless, the significance of thisBIM deletion polymorphism in the resistance to osimertinib has not been reported. Here, we show for the first time that a NSCLC patient harboring theEGFR L858R/T790M mutations, as well as theBIM deletion polymorphism, exhibited poor clinical outcomes with osimertinib treatment. This result suggests that theBIM deletion polymorphism might have prognostic value for determining NSCLC patient outcomes following osimertinib treatment.
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research