scholarly journals Non-small-cell lung cancer: molecular targeted therapy and personalized medicine – drug resistance, mechanisms, and strategies

2013 ◽  
pp. 25 ◽  
Author(s):  
Robert Winn ◽  
Sechler ◽  
Cizmic ◽  
Avasarala ◽  
Van Scoyk ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Personalized Medicine ◽  
Small Cell Lung Cancer ◽  
Molecular Targeted Therapy ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Small Cell Lung ◽  
And Personalized Medicine

scholarly journals 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 ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Targeted Therapies ◽  
Acquired Resistance ◽  
Small Cell ◽  
Tumor Evolution ◽  
Small Cell Lung ◽  
Acquired Drug Resistance

AbstractAcquired drug resistance to even the most effective anti-cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1‒6, the underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. The extent to which therapy actively drives tumor evolution by promoting mutagenic processes7 or simply provides the selective pressure necessary for the outgrowth of drug-resistant clones8 remains an open question. Here, we report that lung cancer targeted therapies commonly used in the clinic induce the expression of cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Induction of A3A facilitated the formation of double-strand DNA breaks (DSBs) in cycling drug-treated cells, and fully resistant clones that evolved from drug-tolerant intermediates exhibited an elevated burden of chromosomal aberrations such as copy number alterations and structural variations. Preventing therapy-induced A3A mutagenesis either by gene deletion or RNAi-mediated suppression delayed the emergence of drug resistance. Finally, we observed accumulation of A3A mutations in lung cancer patients who developed drug resistance after treatment with sequential targeted therapies. These data suggest that induction of A3A mutagenesis in response to targeted therapy treatment may facilitate the development of acquired resistance in non-small-cell lung cancer. Thus, suppressing expression or enzymatic activity of A3A may represent a potential therapeutic strategy to prevent or delay acquired resistance to lung cancer targeted therapy.

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 Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer

2015 ◽  
Vol 11 (1) ◽  
pp. 3-8 ◽  
Author(s):  
GIOVANNA ANTONELLI ◽  
MASSIMO LIBRA ◽  
VINCENZO PANEBIANCO ◽  
ALESSIA ERIKA RUSSO ◽  
FELICE VITO VITALE ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Targeted Therapy ◽  
Small Cell ◽  
Small Cell Lung
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