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Even though a wide range of anticancer agents have been developed, many patients with advanced solid tumors still have a poor prognosis. For the treatment of advanced lung cancer, there are many anticancer agents in clinical use, such as cisplatin, carboplatin, docetaxel, paclitaxel, vinorelbine, gemicitabine, fluorouracil (5FU) derivatives, and irinotecan. A number of combination therapy regimens employing platinum compounds have proven to be effective and are widely applied for the initial treatment of inoperative non-small cell lung cancer (NSCLC). In addition, docetaxel, pemetrexed, and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been reported to be effective in the context of second-line chemotherapy for NSCLC. However, the effect of these therapies on improving patient survival remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities for NSCLC. Recently, molecularly targeted therapy for cancer has made substantial progress. Histone deacetylase (HDAC) inhibitors have been shown to acetylate the nucleosomal histones of condensed chromatin, and cause the reactivation of genes silenced by hyperacetylating histones. HDAC inhibitors, including suberoylanilide hydroxamic acid (SAHA), have demonstrated therapeutic benefits as monotherapy in hematologic, breast, and bladder malignancies, as well as mesothelioma and NSCLC, without evidence of severe adverse events. Recently, it has been demonstrated that combinations of HDAC inhibitors with well-established chemotherapeutic agents have synergistic antitumor effects via the modulation of biomarkers by HDAC inhibitors. We clarified the predictive markers to select patients receiving this treatment and found a new strategy against lung cancer by using the anticancer drug fluorouracil.

journal of nippon medical school

The Anticancer Effect of Histone Deacetylase Inhibitors and Combination with the Cytotoxic Agents in Lung Cancer Cells: Biological Analyses for Future Clinical Application