UF Researchers Say Newly Approved Ovarian Cancer Drugs Cause Mesothelioma Cell Death
In a study at the University of Florida (UF), researchers have discovered that two drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced ovarian cancer also kill malignant pleural mesothelioma cells (MPM). The in vitro study, which appeared in the journal Cancer Chemotherapy and Pharmacology, showed that the two drugs, clinical PARP1 inhibitors known as niraparib and olaparib, markedly decreased clonal survival in all MPM cell lines tested, regardless of BAP1 status. Note that between 23 and 64% of MPMs have somatic inactivating mutations in the BAP1 (BRCA1-associated protein 1) gene.
MPM is a rare and aggressive tumor caused by asbestos exposure. Treatment for the disease is most commonly surgery, with chemotherapy/radiotherapy for residual disease. In the study titled “Synthetic lethality in malignant pleural mesothelioma with PARP1 inhibition,” the researchers wrote, “the prognosis for this disease is dismal, given that complete resection of the tumor is difficult, and the lack of sensitivity to chemotherapy or radiation.”
“PARP1 inhibition at clinically relevant concentrations resulting in significant cytotoxicity in MPM demonstrates that agents such as olaparib and niraparib are promising for use in the treatment of MPM, for which effective treatment is desperately needed. Thus, clinical trials of PARP inhibitors in this difficult to treat malignancy would be warranted.”
Based on a randomized trial of more than 550 patients who had already experienced a recurrence of their high-grade serous ovarian, fallopian tube, or primary peritoneal cancer, niraparib (Zejula) was approved on March 27, 2017 to treat women with advanced ovarian cancer.
On Aug. 17, 2017, the FDA granted regular approval to olaparib tablets (Lynparza, AstraZeneca) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. The approval in the maintenance setting was based on two randomized, placebo-controlled, double-blind, multicenter trials in patients with recurrent ovarian cancers who were in response to platinum-based therapy. The trials consisted of 295 and 265 randomized patients.
UF researchers have hope that niraparib and olaparib will follow the same path and achieve FDA approval for the treatment of MPM.
If you have been diagnosed with mesothelioma, talk to your doctor about clinical trials for promising drugs such as niraparib and olaparib. Innovative therapies such as these could help treat your specific type of mesothelioma.
“Approvals of FDA-Regulated Products.” U.S. Food and Drug Administration (FDA). FDA, 2017. Web. 15 Nov. 2017.
Srinivasan, Gayathri, and Gurjit Singh Sidhu. "Synthetic Lethality in Malignant Pleural Mesothelioma with PARP1 Inhibition." Cancer Chemotherapy and Pharmacology. Springer Berlin Heidelberg, 29 July 2017. Web. 15 Nov. 2017.