Use and mechanism of action of olaparib

Olaparib is a chemotherapeutic agent for patients with recurrent or advanced ovarian and metastatic breast cancer who have specific mutations and a history of previous chemotherapy. “It was originally defined as continuous or monotherapy for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.”

Use and mechanism of action of olaparib

Main uses

“Ovarian cancer, in which the drug is used as maintenance therapy in adult patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have fully or partially responded to platinum-based chemotherapy or who have been treated with three or more prior lines of chemotherapy for advanced ovarian cancer with deleterious or suspected deleterious germline BRCA mutations (gBRCAm).”

“Breast cancer, where the drug is targeted for use in patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2(HER2) -negative metastatic breast cancer who have previously received chemotherapy in a neoadjuvant, adjuvant, or metastatic setting.” Hormone receptor (HR) -positive breast cancer should have received prior endocrine therapy or were deemed to be poor candidates for endocrine therapy.

Mechanism of action

Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes that include PARP1, PARP2, and PARP3. PARP enzymes are involved in benign cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has been shown to inhibit the growth of selected tumor cell lines in vitro and reduce tumor growth in a murine xenograft solid model of human cancer, either as monotherapy or after platinum-based chemotherapy. Elevated cytotoxic and antitumor activity with olaparib has been noted in BRCA-deficient cell lines and mouse tumor models. In vitro studies showed that olaparib-induced cytotoxicity was likely to involve the inhibition of PARP enzyme activity to enhance the production of PARP-DNA complexes, leading to cell stabilization and cell death.