Headlines have hailed the success of cancer immunotherapy—most notably former President Jimmy Carter’s remission in 2015 from melanoma that spread to his brain. “Immuno-oncology is booming,” says Magee- Womens Research Institute investigator Anda Vlad, MD, PhD.
That’s no understatement. Pharmaceutical companies race to put new therapies in the pipeline, and the U.S. Food and Drug Administration has approved immunotherapies for several cancers. Among them are melanoma, prostate cancer, non-small cell lung cancer, and lymphoma.
But missing from the list is ovarian cancer, a malignancy in desperate need of vastly more effective diagnostics and treatment.
“There has been no improvement in three decades,” says Dr. Vlad, an immunologist. “It’s clearly one disease where every effort from every scientist is needed.”
Ovarian cancer is particularly lethal because most times it’s diagnosed at a late stage. Current diagnostics lack accuracy, so the disease rarely is detected early, at stage 1, when the 5-year survival rate is 90 percent or more, says Dr. Vlad. Detection at stage 3 or 4 produces a 5-year survival rate of only about 40 percent.
“If we can catch this cancer early, at the earliest possible stage, we may be able to save a lot of lives,” says Xin Huang, PhD, a Magee-Womens Research Institute investigator who studies tumor cell biology.
To fill the long-standing treatment gap, Dr. Vlad’s lab has laid the foundation to find the most effective mix of traditional chemotherapy drugs and immune boosters to give ovarian cancer patients new optimism. Although she isn’t directly involved in developing new drugs, those treatments couldn’t make their way to patients without her basic science research.
Dr. Vlad develops unique animal models that mimic how the human body responds to ovarian cancer. Some of the models show how tumors spread while others offer clues explaining why some cancers resist chemotherapy. “These animal models are used to test the types of therapies that we want to take to the clinic,” explains Dr. Vlad.
Her animal data helped launch a phase 1 clinical trial at Magee-Womens Hospital of UPMC, where fellow immunologists and gynecology-oncology surgeons evaluate the safety of combining the traditional platinum- based chemotherapy drug with the immune- boosting drug rintatolimod. Some patients in the trial also receive interferon alpha, another potent immune stimulant.
The drugs are delivered through a catheter directly into the peritoneal cavity, where ovarian cancer cells often migrate. The hope is that during phase 2 of the trial, results will show that chemotherapy and immunotherapy administered directly to the tumor cell environment will join forces to wipe out the cancer. Treatment with a single drug typically isn’t enough to combat ovarian cancer, Dr. Vlad notes. “Combination therapies are the way to go,” she says.
But treatment without accurate diagnostics for early detection is a glass half empty. That’s where Dr. Huang comes in. Research in his lab goes hand-in-hand with Dr. Vlad’s studies by working to identify biomarkers that could be early signatures of ovarian cancer. To do that, he uses Dr. Vlad’s models as well as animal models recently developed in his own lab.
Dr. Huang has had some success on the biomarker front. He and Dr. Vlad were co- authors of published research that showed tiny bits of genetic material called microRNAs that circulate in the blood could distinguish between healthy women and those who had benign endometriosis or endometriosis- associated ovarian cancer.
Both researchers are interested in the growing evidence that shows a link between ovarian cancer and endometriosis, the atypical growth of uterine tissue outside of the uterus.
“Some of those benign lesions actually can progress to cancer,” says Dr. Vlad. The National Institutes of Health reports that an estimated 5 million women in the U.S. have endometriosis, but that may be an underestimate because the condition often remains undiagnosed.
That makes finding a biomarker for endometriosis-associated ovarian cancer all the more important. Many women don’t know they have the condition and so aren’t aware that their risk of developing ovarian cancer is elevated. Dr. Huang’s goal is to find a biomarker that accurately detects ovarian cancer with a simple blood test. “That is the gold standard,” he says.
Looking toward the future, ovarian cancer research at Magee-Womens Research Institute has implications for precision medicine—the concept of tailoring medical care for each patient based on their individual characteristics.
Dr. Huang’s work in biomarkers fits that bill while Dr. Vlad’s research also includes work on a personalized ovarian cancer vaccine based on antigens from individual patients’ own tumors.
The ongoing fight against ovarian cancer, Dr. Vlad says, is “a constant struggle” to push science forward, obtain research funding, and design new clinical trials.
“But there is hope,” she adds. “We are on the right track.”
To learn more about Dr. Vlad’s and Dr. Huang’s research, click the links below.
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