RNA interference against polo-like kinase-1 in advanced non-small cell lung cancers

RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in mammalian cells and its discovery has lead to its wide application as a powerful tool in post-genomic research. Recently, short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Recently, several clinical trials of RNAi therapies against cancers are ongoing. In this article, we discuss the most recent findings concerning the administration of siRNA against polo-like kinase-1 (PLK-1) to liver metastatic NSCLC. PLK-1 regulates the mitotic process in mammalian cells. These promising results demonstrate that PLK-1 is a suitable target for advanced NSCLC therapy.Worldwide, approximately one and a half million new cases of lung cancer are diagnosed each year [1]. About 85% of lung cancer are non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell, and large cell carcinoma [2], and NSCLC is the leading cause of cancer-related deaths. Surgery is generally regarded as the best strategy for lung cancers. However, only 30% of patients are suitable for receiving potentially curative resection [3], and it is necessary for other patients to be treated with chemotherapy. As we gain a better understanding of the molecular pathogenesis underlying NSCLC, new molecular targeting agents can be developed. Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR), such as gefitinib and erlotinib, have shown remarkable activity in the patients with NSCLC, and particularly these TKIs are more effective to NSCLC with EGFR mutations in 19 exon (in-frame deletions) and exon 21 (L858R point mutation), which are found to be more prevalent in Asian patients [4,5]. However, despite the development of new TKIs, new mutations in EGFR exon 20, developing resistance to EGFR TKIs, have emerged in the treated NSCLC [6,7], and current therapies are not sufficient