PARP Inhibitors in Small-Cell Lung Cancer: Rational Combinations to Improve Responses

摘要

Small-cell lung cancer carries a dismal prognosis with few long-term treatment options. The enzyme poly-(ADP)-ribose polymerase (PARP), which functions to repair DNA breaks, has emerged as a promising therapeutic target, with modest response rates in early clinical trials prompting investigation of predictive biomarkers and therapeutic combinations. This review summarizes the development and testing of PARP inhibitors in small-cell lung cancer with an emphasis on developing treatment combinations. These combinations can be divided into three categories: (1) contributing to DNA damage; (2) inhibiting the DNA damage response; and (3) activating the immune system. An evolving classification of small-cell lung cancer subtypes and gene expression patterns will guide PARP inhibitor biomarker identification to improve treatments for this challenging cancer.