Intracellular Pharmacokinetics of PARP Inhibitors in Breast and Ovarian Cancer Cells and Correlation to Drug Action: A Review

Recently Poly (ADP-Ribose) Polymerase inhibitor (PARPi) drugs were approved by the FDA for clinical use in breast and ovarian cancer, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Olaparib an oral formulation approved for the treatment of patients with BRCA mutation and recurrent ovarian cancer; has shown to provide clinically significant benefit. Inhibition of PARP results in accumulation of single-strand breaks, leading to formation of double-strand breaks. Olaparib, a small molecule, selectively binds and inhibits Poly (ADP-Ribose) Polymerase enzyme, inhibiting its mediated repair of single-strand DNA breaks. Poly (ADP-Ribose) Polymerase inhibition enhances cytotoxicity of DNA damaging agents and reverses tumor cell chemoresistance and radio resistance. There has been limited research on the quantification of anti-cancer drugs intracellularly; very few studies have attempted to quantify Olaparib intracellularly. For the first time, intercellular quantification of PARP inhibitor was reported in two studies involving oral dosage form and the other nano-delivery system, allowing for quantification of Olaparib distribution in the nuclei, cytoplasm, liver, kidney, plasma, and urine. This review, covers articles and reports from 1992 to 2019 and is aimed at highlighting the increasing importance of intracellular quantification of anti-cancer drugs using PARP inhibitors as examples, due to limited research done on this group of drugs, only Olaparib has been reported have been determined intracellularly.