MicroRNAs Involved in Small-cell Lung Cancer as Possible Agents for Treatment and Identification of New Targets

Abstract

Small-cell lung cancer, a neuro-endocrine type of lung cancers, responds very well to chemotherapy-based agents. However, a high frequency of relapse due to adaptive resistance is observed. Immunotherapy-based treatments with checkpoint inhibitors has resulted in improvement of treatment but the responses are not as impressive as in other types of tumor. Therefore, identification of new targets and treatment modalities is an important issue. After searching the literature, we identified eight down-regulated microRNAs involved in radiation-and chemotherapy-induced resistance, as well as three up-regulated and four down-regulated miRNAs with impacts on proliferation, invasion and apoptosis of small-cell lung cancer cells in vitro. Furthermore, one upregulated and four down-regulated microRNAs with in vivo activity in SCLC cell xenografts were identified. The identified microRNAs are candidates for inhibition or reconstitution therapy. The corresponding targets are candidates for inhibition or functional reconstitution with antibody-based moieties or small molecules.Small-cell lung cancer (SCLC) is an exceptionally lethal malignancy comprising 13-15% of all lung cancer (1), with 250,000 cases diagnosed annually worldwide (1). SCLC is highly sensitive to platinum-based chemotherapy, topoisomerase inhibitor etoposide, and to lurbinectidin, a recently approved DNA binder (2, 3). However, disease 591 This article is freely accessible online.

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