Related Experiment Video
Updated: Nov 26, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Clinical implications of germline BCL2L11 deletion polymorphism in pretreated advanced NSCLC patients with
Xuanzong Li1, Dai Zhang2, Butuo Li3
1Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Introduction:
B-cell lymphoma 2-like 11 (BCL-2-like 11, BCL2L11, also known as BIM) deletion polymorphism (BIM-del) has been associated with resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and is a poor prognostic factor for EGFR-mutant non-small-cell lung cancer (NSCLC) patients. Nevertheless, the impact of BIM-del in advanced NSCLC patients treated with the third-generation EGFR-TKI osimertinib remains undetermined. This study aims to evaluate the relationship between BIM-del and therapeutic efficacy of osimertinib in pretreated NSCLC patients.
Methods:
Patients subjected to EGFR T790 M detection and prior osimertinib treatment between December 2015 and December 2019 in our hospital were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del.
Results:
In total, 152 Chinese Han NSCLC patients-including 143 T790M-positive and nine T790M-negative patients-were enrolled. BIM-del was detected in only 17.5 % of T790M-positive patients (25/143). The majority of patients were aged <65 years (81.8 %, 117/143), were female (58.7 %, 84/143), were non-smokers (82.5 %, 118/143), had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (88.8 %, 129/143), and exhibited metastases in the central nervous system (CNS) (54.5 %, 78/143). There were no associations between the BIM-del and clinical characteristics (including age, sex, histology, smoking status, stage, ECOG PS score, and CNS metastases). Patients with BIM-del had a poorer objective response rate than those without (28.0 % versus 52.5 %, p = 0.026). Besides, BIM-del was associated with a significantly shorter progression-free survival (PFS) and a moderately shorter overall survival (OS) (8.3 versus 10.5 months, p = 0.031 and 15.9 versus 25.2 months, p = 0.1, respectively). Multivariate analysis indicated that BIM-del was an independent prognostic factor for PFS but not for OS in EGFR T790 M NSCLC patients.
Conclusions:
BIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment.
Insights
The B-cell lymphoma 2-like 11 (BCL2L11, BIM) deletion polymorphism (BIM-del) is linked to poorer outcomes in non-small-cell lung cancer (NSCLC) patients treated with osimertinib. BIM-del may serve as a negative predictive biomarker for treatment efficacy.
Area of Science:
- Oncology
- Genetics
- Pharmacogenomics
Background:
- The B-cell lymphoma 2-like 11 (BCL2L11, BIM) deletion polymorphism (BIM-del) is associated with resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) and predicts poor prognosis in EGFR-mutant non-small-cell lung cancer (NSCLC).
- The clinical impact of BIM-del on patients receiving third-generation EGFR-TKI osimertinib remains unclear.
Purpose of the Study:
- To investigate the association between BIM-del and the therapeutic efficacy of osimertinib in pretreated advanced NSCLC patients.
- To evaluate BIM-del as a predictive and prognostic biomarker in this patient cohort.
Main Methods:
- Retrospective analysis of 152 Chinese Han NSCLC patients treated with osimertinib after EGFR T790M detection.
- BIM-del detection in peripheral blood using polymerase chain reaction.
- Clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were analyzed using Cox proportional hazards models.
Main Results:
- BIM-del was detected in 17.5% of T790M-positive patients and showed no association with clinical characteristics.
- Patients with BIM-del exhibited a significantly lower ORR (28.0% vs. 52.5%, p=0.026) compared to those without.
- BIM-del was associated with shorter PFS (8.3 vs. 10.5 months, p=0.031) and a trend towards shorter OS (15.9 vs. 25.2 months, p=0.1).
- Multivariate analysis identified BIM-del as an independent prognostic factor for PFS in EGFR T790M NSCLC patients.
Conclusions:
- BIM-del is associated with poor clinical response and outcomes in NSCLC patients treated with osimertinib.
- BIM-del may function as a negative predictive and prognostic biomarker for osimertinib efficacy in EGFR T790M-positive NSCLC.
More Related Videos
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...