The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non–Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors

Lee, Ji Yun; Ku, Bo Mi; Lim, Sung Hee; Lee, Min Young; Kim, Haesu; Kim, Moonjin; Kim, Sung-Min; Jung, Hyun Ae; Sun, Jong Mu; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung Ju

doi:10.1097/jto.0000000000000535

Cited by 34 publications

(38 citation statements)

References 49 publications

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“…Our study documented for the first time the prevalence of BIM deletion polymorphism in the Latin American population (15.7 %; 14 of 89 patients). This prevalence is similar to that previously reported in the Asian population [24–26, 28]. We did not analyze the prevalence of BIM deletion polymorphism in healthy volunteers.…”

Section: Discussionsupporting

confidence: 87%

“…In the literature there are other studies with contradictory results to our study, failing to demonstrate an association between BIM deletion polymorphism and the response to EGFR TKI therapy [26, 28]. For example, Lee et al analyzed the influence of BIM deletion polymorphism in 205 NSCLC EGFR mutation positive patients [28].…”

Section: Discussioncontrasting

confidence: 75%

“…Several studies have demonstrated that BIM deletion polymorphism is related with response to EGFR TKIs in NSCLC [20, 24–28]. BIM deletion polymorphism is an independent predictive factor of response to EGRF TKIs.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Lee et al analyzed the influence of BIM deletion polymorphism in 205 NSCLC EGFR mutation positive patients [28]. BIM del+ patients had similar objective response rates compared to BIM del- patients (91% vs. 84%, p = 0.585).…”

Section: Discussionmentioning

confidence: 99%

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BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

et al. 2016

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Background: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-smallcell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations.Results: BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIMdel; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006).Methods: We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded

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Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

et al. 2016

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“…Two retrospective studies failed to observe an association between BIM genotype and response rates to PKIs in NSCLC patients (Lee et al, 2013; Lee et al, 2015a). However, a systematic review and meta-analysis of 951 patients supported the BIM deletion polymorphism as a predictor of shorter progression free survival (PFS) in NSCLC patients who were treated with PKIs (adjusted HR = 2.38, p < 0.001) (Nie et al, 2015).…”

Section: Germline Pharmacogenomics As a Mechanism Of Pharmacological mentioning

confidence: 99%

The pharmacogenomics of drug resistance to protein kinase inhibitors

Gillis

McLeod

2016

Drug Resistance Updates

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Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. This reveals a role for pharmacogenomic analysis to identify and monitor for resistance, with possible therapeutic strategies to combat chemoresistance.

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Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion‐positive non–small cell lung cancer

Zhang

Jiang

et al. 2017

Cancer

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The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non–Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors

Abstract: It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.

Cited by 34 publications

References 49 publications

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

The pharmacogenomics of drug resistance to protein kinase inhibitors

Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion‐positive non–small cell lung cancer

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