scholarly journals Drug resistance analysis of gefitinib-targeted therapy in non-small cell lung cancer

2016 ◽  
Vol 12 (5) ◽  
pp. 3941-3943 ◽  
Author(s):  
Shuliang Liu ◽  
Hongji Yang ◽  
Xingping Ge ◽  
Lingfei Su ◽  
Aifeng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resistance Analysis

scholarly journals Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Walter Z. Wang ◽  
Konstantin Shilo ◽  
Joseph M. Amann ◽  
Alyssa Shulman ◽  
Mohammad Hojjat-Farsangi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Therapeutic Target ◽  
Small Cell ◽  
Orphan Receptor ◽  
Small Cell Lung ◽  
Sclc Patient

AbstractSmall cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.

circSNX6 (hsa_circ_0031608) enhances drug resistance of non-small cell lung cancer (NSCLC) via miR-137

2021 ◽  
Vol 567 ◽  
pp. 79-85
Author(s):  
Koujun Zhu ◽  
Jun Zhu ◽  
Jichun Geng ◽  
Yongjian Zhang ◽  
Yan Qin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Expression Profiles of microRNAs in Drug-Resistant Non-Small Cell Lung Cancer Cell Lines Using microRNA Sequencing

2018 ◽  
Vol 51 (6) ◽  
pp. 2509-2522 ◽  
Author(s):  
Shousen Hu ◽  
Yongliang Yuan ◽  
Zhizhen Song ◽  
Dan Yan ◽  
Xiangzhen Kong
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Nsclc Cell ◽  
Drug Resistant ◽  
Small Cell Lung

Background/Aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines. Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Results: A total of 29 upregulated miRNAs and 36 downregulated miRNAs were found in the drug-resistant NSCLC cell lines, of which 26 upregulated and 36 downregulated miRNAs were found to be involved in the Ras signaling pathway. The expression levels, survival analysis, and receiver operating characteristic curve of the dysregulated miRNAs based on The Cancer Genome Atlas database for lung adenocarcinoma showed that hsa-mir-192, hsa-mir-1293, hsa-mir-194, hsa-mir-561, hsa-mir-205, hsa-mir-30a, and hsa-mir-30c were related to lung cancer, whereas only hsa-mir-1293 and hsa-mir-561 were not involved in drug resistance. Conclusion: The results of this study may provide novel biomarkers for drug resistance in NSCLC and potential therapies for overcoming drug resistance, and may also reveal the potential mechanisms underlying drug resistance in this disease.

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