July 13, 2017
Even though ovarian cancer makes up only 1.3 percent of new cancer diagnoses in the U.S., the disease is the fifth-leading cause of cancer-related deaths in U.S. women, according to the National Cancer Institute. Up to 85 percent of women experience recurrence of ovarian cancer after standard chemotherapy, which utilizes a drug called carboplatin.
Researchers have recently discovered a promising combination of chemotherapy which involves combining the experimental drug birinapant with standard carboplatin. Birinapant degrades a type of protein called cIAPs. cIAPs prevent cell death after chemotherapy. Carboplatin-resistant ovarian cancer stem cells contain high levels of cIAPs, but if birinapant degrades the proteins, carboplatin may be more effective.
Testing in mice revealed that while birinapant or carboplatin alone had minimal effect, the combination therapy doubled overall survival in half of the mice. Then, using samples from serious ovarian cancer tumors from patients (including patients who had never been treated or who were known to have carboplatin-resistant cancer), researchers discovered a strong correlation between cancer stem cells with high levels of cIAPs and positive response to the combination therapy.
Disease-in-a-dish models were then created using human bladder, cervix, colon, and lung cancer cells. The combination therapy correlated positively in treating 50 percent of the tumors.
Carboplatin is a platinum drug, meaning it contains derivatives of the metal platinum. Typically, platinum drugs are identifiable by the “-platin” suffix at the end of their names, like carboplatin. These platinum drugs are “the frontline therapy in many carcinomas, including high-grade serious ovarian cancers,” according to an article by University of California Los Angeles and University of California Berkeley researchers.
Various cancers react strongly to drugs like carboplatin, but tumors invariably recur and their response to platinum drugs diminishes over time. Standard of care prohibits re-administration of platinum drugs to patients, but researchers argue that this practice should be challenged because “platinum drugs can be an effective therapy even for platinum-resistant carcinomas as long as they are combined with an agent that specifically targets mechanisms of platinum resistance exploited by the therapy-resistant tumor sub-populations.” In other words, a combination therapy like the carboplatin-birinapant mix should, researchers argue, be made available to patients who have already undergone carboplatin chemotherapy.