In this review, we will discuss cancer-related functions of PARP-1 – including regulation of inflammatory mediators through NF-κB, cell death and energetics, ERK-mediated tumor progression and invasion, mitosis, gene transcription, and sex hormone signaling – and examples of how these functions may be exploited to expand the patient population potentially benefiting from treatment with PARP inhibitors. This evidence concerns the gene MAPK1 and neoplasm.