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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Imprimer: 0893-9675
ISSN En ligne: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2013007191
pages 317-326

Molecular Mechanisms Underlying the Role of MicroRNAs in Resistance to Epidermal Growth Factor Receptor-Targeted Agents and Novel Therapeutic Strategies for Treatment of Non-Small-Cell Lung Cancer

Mina Maftouh
Department of Medical Oncology, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV
Amir Avan
Department of Medical Oncology, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV
Elena Galvani
Department of Medical Oncology, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV
Godefridus J. Peters
Department of Medical Oncology, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV
Elisa Giovannetti
Department of Medical Oncology, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV

RÉSUMÉ

Non–small cell lung cancer (NSCLC) is one of the deadliest types of cancer. One explanation for this poor prognosis is the failure of most chemotherapeutic regimens, which prompted the development of new, rationally designed, targeted antitumor agents, such as inhibitors of the epidermal growth factor receptor (EGFR) and downstream pathways. However, most of these targeted therapies also fail, and studies on the mechanisms underlying resistance toward targeted agents might provide critical findings for NSCLC research and treatment. Some of these studies showed that drug resistance can emerge not only from genetic aberrations, but also from epigenetic changes, including regulation of different signaling pathways by microRNAs (miRNAs), which act as key post-transcriptional regulators of gene expression. There is accumulating evidence that specific miRNAs correlated with drug sensitivity and can be used as prognostic markers in NSCLC. However, a greater knowledge of miRNAs might also provide novel insights in several drug-resistance mechanisms; hence, suggesting their potential in novel therapeutic interventions, by sensitizing tumor cells to drug-induced apoptosis as well as by inhibiting tumor proliferation and invasive capabilities. Therefore, this review highlights several recent and clinically relevant aspects of the regulation of drug resistance by miRNAs from the perspective of current anti-EGFR–targeted therapies in NSCLC.