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

ABSTRACT: Despite recent advances in first-line treatment for small-cell lung cancer (SCLC), durable responses remain rare. The DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) was identified as a therapeutic target in SCLC using unbiased preclinical screens and confirmed in human and mouse models. Early trials of PARP inhibitors, either alone or in combination with chemotherapy, showed promising but limited responses, suggesting that selecting patient subsets and treatment combinations will prove critical to further clinical development. Expression of SLFN11 and other components of the DNA damage response (DDR) pathway appears to select for improved responses. Combining PARP inhibitors with agents that damage DNA and inhibit DDR appears particularly effective in preclinical and early trial dat

SUBMITTER: Knelson EH 

PROVIDER: S-EPMC7916546 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature