scholarly journals Identification of Hub Genes and Small Molecule Drugs Associated with Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer

2021 ◽  
Vol 12 (17) ◽  
pp. 5286-5295
Author(s):  
Guangda Li ◽  
Yunfei Ma ◽  
Mingwei Yu ◽  
Xiaoxiao Li ◽  
Xinjie Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Small Molecule Drugs

scholarly journals Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation

2020 ◽  
Vol 16 (21) ◽  
pp. 1537-1547
Author(s):  
Fumio Imamura ◽  
Madoka Kimura ◽  
Yukihiro Yano ◽  
Masahide Mori ◽  
Hidekazu Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Clinical Trial Registration

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry)

scholarly journals Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Kaili Long ◽  
Lili Gu ◽  
Lulu Li ◽  
Ziyu Zhang ◽  
Enjie Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Molecular Compound ◽  
Small Cell Lung

AbstractApurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.

Abstract 39: APOBEC3A drives acquired resistance to targeted therapies in non small cell lung cancer

2021 ◽  
Author(s):  
Hideko Isozaki ◽  
Ammal Abbasi ◽  
Naveed Nikpour ◽  
Adam Langenbucher ◽  
Wenjia Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung

Characterising acquired resistance to erlotinib in non-small cell lung cancer patients

2019 ◽  
Vol 13 (10) ◽  
pp. 1019-1028 ◽  
Author(s):  
Niki Karachaliou ◽  
Jordi Codony-Servat ◽  
Jillian Wilhelmina Paulina Bracht ◽  
Masaoki Ito ◽  
Martyna Filipska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients
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