Up to 85 percent of women experience recurrence of high-grade serous ovarian cancer — the most common subtype of ovarian cancer — after standard treatment with the chemotherapy drug carboplatin.

Why?

New research out of UCLA may contain the answer, as well as a new and more effective way to treat the disease.

The scientists discovered that certain carboplatin-resistant ovarian cancer cells contained high levels of proteins called cIAPs, which prevent cell death after chemotherapy. Because these cells could survive the chemo treatment while all their neighbors perished, they would subsequently regenerate the tumor.

The researchers began experimenting with birnapant, a drug which degrades cIAPs and can make carboplatin more effective against some ovarian cancer tumors. But although birnapant was effective in ways that carboplatin was not, neither was improving overall ovarian cancer survivability on their own.

In their latest work, the researchers first tested whether a combination of of carboplatin and birnapant could improve survival in mice. Half of the mice tested had carboplatin-resistant human ovarian cancer tumors and the other half had carboplatin-sensitive tumors. The team administered birinapant or carboplatin as well as the two drugs combined and then monitored the mice over time. While either drug alone had minimal effect, the combination therapy doubled overall survival in half of the mice regardless of whether they had carboplatin-resistant or carboplatin-sensitive tumors

The team then upped their game by testing 23 high-grade serous ovarian cancer tumors from independent patients. Some were from patients who had never been treated with carboplatin and some were from patients who had carboplatin-resistant cancer.

With these samples, the scientists generated ovarian cancer tumors using a method called disease-in-a-dish modeling and tested the same treatments previously tested in mice. Again, carboplatin or birinapant alone had some effect, but the combination of birinapant and carboplatin successfully eliminated the ovarian cancer tumors in approximately 50 percent of samples. Most importantly, the combination therapy worked for both carboplatin-resistant and carboplatin-sensitive tumors.

The researchers later created disease-in-a-dish models using human bladder, cervix, colon and lung cancer cells and tested the combination therapy. As with their ovarian cancer findings, 50 percent of the tumors were effectively targeted and high cIAP levels correlated with a positive response to the combination therapy.

The research has been published in Precision Oncology.