BRCA1 and cancer: For example, while PARP1 loss-of-function mutations were initially discovered to be synthetically lethal with BRCA1 and BRCA2 mutations [14], some cancer patients with such mutations have not benefited from PARP1 inhibition [65], and many tumors that are BRCA1- and BRCA2-proficient can likewise be sensitized by PARP1 inhibition [66, 67].