OCRA-Funded Study Discovers Potential Target for Overcoming Treatment Resistance 

Snap Summary: An OCRA-funded study sought to understand why certain ovarian cancer cells resist olaparib treatment, and discovered that introducing a second drug (mifepristone) while targeting certain cells (polyploid giant cancer cells) may offer a solution.

In a study published in the journal Science Advances, researchers at MD Anderson Cancer Center set their sights on PARP inhibitor resistance in the most common subtype of ovarian cancer, high-grade serous carcinomas (HGSCs), and made a significant breakthrough.

Co-led by Jinsong Liu, MD, PhD, and Anil K. Sood, MD, an OCRA grantee and Scientific Advisory Committee member, the team at MD Anderson Cancer Center sought to better understand polyploid giant cancer cells’ (PGCCs) role in ovarian cancer treatment resistance.

Dr. Liu and his team have studied the role of PGGCs in ovarian cancer for the past decade. His team showed that PGCCs have properties akin to “embryos” that can fuel treatment resistance, but their relationship to olaparib resistance in ovarian cancer isn’t fully understood. 

In this new study, working with a range of ovarian cancer cells, with and without BRCA mutations, researchers found that PGCCs appeared more often in all tumors that were resistant to olaparib. Although targeting PGCCs with olaparib did typically cause them to stop dividing for a short time, they later gave rise to more olaparib-resistant cells. 

Encouragingly, researchers found that introducing another drug called mifepristone, a commonly used contraceptive drug, to the olaparib treatment targeting PGCCs successfully halted the cancer’s progression and eradicated the tumors in lab models.

This discovery is a promising step forward in overcoming treatment resistance in patients with ovarian cancer.

“This work provides the first experimental proof of our long-standing hypothesis that blocking the embryogenic process induced by the therapeutic stress can potentially increase the therapeutic efficacy and combat the resistance in ovarian cancer,” said Dr. Liu of the promising results.

“Although the current work was preclinical, we feel that it provides important evidence to conduct clinical trials to target the PGCCs to enhance the effects of PARP inhibitors,” added Dr. Sood.

“The support from OCRA is so important for us to develop new ideas and position the team for seeking additional support to expand the work and translate the findings into the clinic.”

Read more in Science Advances.