Despite the encouraging therapeuticbenefits of PARPi, these agents show some critical issues, such assuboptimal clinical efficacy, ineffectiveness in certain DNA-repairdeficient cancers, and development of acquired and innate resistance.54,55 The major resistance mechanism observed in preclinical and clinicalmodels was related to the reversion mutation in BRCA2, which allows the correct encoding of functional proteins, thusrestoring the HR pathway. This evidence concerns the gene BRCA2 and cancer.