Evaluation of phototoxicity induced by the anticancer drug rucaparib

Rucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. It is used for the treatment of breast and ovarian tumors harboring deleterious germline or somatic cancer susceptibility genes mutations. Although RCP has an indole chromophore in its structure, it displays a bathochromic shift of the absorption band towards the UVA region of sunlight, thus extending the active fraction of solar light able to produce photosensitivity reactions. In this context, it is highly interesting to study the photo(geno)toxicity disorders associated with this drug, bearing in mind that, for dermatologists it is crucial to understand the toxicity mechanism to improve clinical management. In the present work, RCP has shown to be potentially phototoxic, as observed in the neutral red uptake phototoxicity test. Moreover, this significant phototoxicity is attributed to both proteins and genomic DNA, as revealed in the protein photooxidation and comet assays. The results obtained are highly relevant concerning RCP photosafety and become clinically important in the context of identification of the cutaneous adverse events that can be associated with the targeted therapies. Interestingly, this is the first example of a PARP inhibitor able to induce photosensitized damage to biomolecules.