Implications of MicroRNAs in the Treatment of Gefitinib-Resistant Non-Small Cell Lung Cancer

Autor: S. C. Cesar Wong, William C. Cho, Fengfeng Wang, Fei Meng, Parco M. Siu, Thomas K. Sin, Lawrence W. C. Chan, Benjamin Yat-Ming Yung
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Lung Neoplasms
medicine.medical_treatment
gefitinib
Review
Pharmacology
Targeted therapy
lcsh:Chemistry
0302 clinical medicine
Epidermal growth factor
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
lcsh:QH301-705.5
Spectroscopy
Kinase
Drug Synergism
General Medicine
Computer Science Applications
ErbB Receptors
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Signal transduction
medicine.drug
EGFR
Antineoplastic Agents
Catalysis
Inorganic Chemistry
resistance
03 medical and health sciences
Gefitinib
Cell Line
Tumor
microRNA
medicine
Animals
Humans
Physical and Theoretical Chemistry
Lung cancer
Molecular Biology
Protein Kinase Inhibitors
PI3K/AKT/mTOR pathway
non-small cell lung cancer
miRNA
Biological Products
business.industry
Organic Chemistry
medicine.disease
respiratory tract diseases
MicroRNAs
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Drug Resistance
Neoplasm
Mutation
Cancer research
Quinazolines
business
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 17, Iss 2, p 237 (2016)
ISSN: 1422-0067
Popis: Non-small cell lung cancer (NSCLC) represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs) negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally-induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations.
Databáze: OpenAIRE
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