Genomic profiling of small-cell lung cancer: the era of targeted therapies

The molecular profiling of small-cell lung cancer is challenging because of the difficulty in obtaining suitable tumor samples for integrative genomic analysis. While an urgent need exists for well-defined and effective therapeutic targets in small-cell lung cancer, no significant improvement has been made in treating this disease over the past 30 years. Recently, three reports describing comprehensive genomic analyses of small-cell lung cancer have been published. These reports have provided a framework of biologically relevant genes in small-cell lung cancer and have demonstrated that the genomic landscape of small-cell lung cancer was almost equivalent between Asian and Caucasian populations. Of note, these three comprehensive genomic analyses and other molecular analyses of small-cell lung cancer have contributed to the identification of patient populations that may benefit from promising targeted agents, such as those affecting the PI3K/AKT/mTOR pathway, FGFR1, RET or AURORA kinase inhibitors. Targeting small-cell lung cancer cells with tumor suppressor gene alteration based on synthetic lethality is also promising. The present review provides an overview of the biologically relevant genetic alterations and targeted therapies of small-cell lung cancer focusing on recent discoveries that could impact the management of small-cell lung cancer.