Finding may lead to personalized ovarian, brain cancer therapy

Volume 7, Issue 3, 2018


Researchers discovered a molecular communication pathway has a key role in oncolytic virus therapy.

Evanthia Galanis, M.D.

Evanthia Galanis, M.D.

Mayo Clinic researchers have discovered that a molecular communication pathway thought to be defective in cancer is a key player in determining the effectiveness of a cancer treatment that employs a form of the measles virus to treat aggressive ovarian cancer and brain cancer.

The discovery has enabled researchers to develop an algorithm to predict treatment effectiveness in individual patients. The findings on oncolytic virotherapy were published in the Journal of the National Cancer Institute.

"This discovery will allow us to personalize cancer treatment by matching the most appropriate patients with oncolytic virus therapies," said Evanthia Galanis, M.D., an oncologist at Mayo Clinic in Rochester, Minnesota, and senior author of the published study. "We'll also know which ones can be helped by combining cancer virotherapy with other immune approaches."

The molecular communication pathway, known as the interferon response pathway, had been considered defective in cancer cells. But that isn't the case, the research team found. They performed tests for gene variants and signatures that would identify pathways that resisted the effectiveness of the virus-based treatments that Mayo Clinic has long been developing.

The researchers tested their algorithm on patients and human ovarian tumors and brain tumors transplanted into mice in phase I clinical trials. They discovered a weighted gene signature that could predict treatment sensitivity and resistance. Subsequent research also showed that repurposing ruxolitinib, a drug approved to treat blood cancer, was able to overcome the treatment resistance. Ruxolitinib, which targets the interferon response pathway, allows the measles virotherapy to increase effectiveness by a factor of 1,000.

The researchers say these findings will help them select patients for future clinical trials involving oncolytic viruses and help shape how those viruses are designed and used in medicine, including the development of effective combination therapies.