Translational Center of Excellence offers hope in the fight against the deadliest gynecologic cancer.
In the United States, about 20,000 women are diagnosed each year with ovarian cancer, an often silent disease that’s largely free of symptoms until it spreads, making it more difficult to treat. Ovarian cancer ranks fifth in cancer deaths among women and accounts for more deaths than any other gynecologic cancer.
"It's not the most common cancer, but it's one of the most difficult to cure” said Mark A. Morgan, MD, chief of the Division of Gynecologic Oncology. “…it's a challenge because patients often respond to treatment initially but frequently become resistant to therapy, and then eventually die of their disease.
“So, we're able to make an impact, but the ultimate cure is elusive.”
The Ovarian Cancer Research Center (OCRC), under the co-leadership of Ronny Drapkin, MD, PhD, was recently awarded a Translational Center for Excellence (TCE) grant from the Abramson Cancer Center. Dr. Drapkin is co-leading the TCE with Fiona Simpkins, MD. With additional support from the Department of Obstetrics and Gynecology, the OCRC is expanding its infrastructure to create a resource for research within Penn Medicine, as well as nationally and internationally.
"The TCE provides the infrastructure that will enable us to follow patients over time and collect, store and study tumor samples from initial diagnosis through each recurrence," Dr. Drapkin said. "The TCE will study how ovarian cancer evolves from being sensitive to chemotherapy treatment to eventually recurring and becoming resistant.
From Lab to Clinic
“You can't have a Translational Center of Excellence unless you can take those discoveries and get them into the clinic,” Dr. Morgan said. “Our program is unique because we have tried to eliminate the separation between routine clinical practice and research – we integrate research into everything we do and strongly believe that good clinical care involves research.”
“With cancer, that's more true than ever.”
Although ovarian cancer is usually very responsive to therapy initially, most patients require multiple therapies, including surgery, chemotherapy, immunotherapy and targeted therapy.
“That's why we need to have both standard therapies and research protocols to utilize,” Dr. Morgan said. “Our patients are frequently enrolled in a clinical trial, and then return to a standard therapy and vice versa. They just keep moving along in one seamless program.”
The TCE plays a critical role – it links the investigators who develop therapies in the lab with the clinical care we provide in the practice and hospital. It allows us to rapidly translate new therapies into Phase 1 and Phase 2 clinical trials.
“We have therapeutic trials that are investigator-initiated, and we also have prevention trials available at Penn Medicine,” said Fiona Simpkins, MD, associate professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania and co-director of the TCE. “The goal is to provide patients with new therapeutic options. It’s an exciting time at the Ovarian Cancer Research Center, where scientists are evaluating ways to prevent and treat ovarian cancers, from the bench to the patient’s bedside.”
Expanding Tumor Banking
One cornerstone of the TCE involves collecting living tumor tissue from patients cared for by gynecologic oncologists across the health system.
Tumor samples are currently being collected near the time of diagnosis and cancer recurrence – at the Hospital of the University of Pennsylvania, Pennsylvania Hospital and Chester County Hospital. Those samples become part of the OCRC Tumor BioTrust and are used to study how ovarian cancer evolves over time with the goal of discovering more effective treatment options.
“We've named it the BioTrust Collection, because patients entrust their tissues to us,” Dr. Drapkin said. “We owe it to our patients to do as much as we can with the tissues they entrust to us. It’s one of our missions.”
Using Banked Tissues
Once the tissues are collected, they are used to develop patient-derived tumor xenografts (PDX), by implanting and growing a portion of the patient’s tumor into a mouse.
“We think those are the best models around to really understand human ovarian carcinoma,” Dr. Drapkin said.
Dr. Simpkins uses PDX models to test combination therapies for ovarian cancer.
“I am uniquely positioned as someone who takes care of patients in the operating room and the clinic,” she said. “Understanding the unanswered clinical questions gets me excited to go to the lab to try to develop a cure for ovarian cancer.”
“Ovarian cancer patients run out of treatment options, and when I see that patient sitting in my office and there is nothing left to offer her, that drives me to go back to the lab at 5 p.m. and on weekends to try to develop new therapies.”
And Dr. Simpkins has had successes in the lab.
PARP inhibitors, new drugs which kill cancer cells by limiting their ability to repair damaged DNA, work well in treating patients with hereditary ovarian cancer. Dr. Simpkins and scientists in her lab found that PARP inhibitors work better when combined with another class of drugs called ATR inhibitors, which also affect cancer cells’ ability to repair their DNA. The evidence found using PDX models in the lab supported moving the combined therapy into a Phase 1 and 2 clinical trial for the treatment of recurrent ovarian cancer. So far, 12 patients have been enrolled.
“The ultimate goal is to prevent the cancer from coming back,” Dr. Simpkins said. “We have also identified other exciting new combinations in the laboratory that we hope to move forward in the clinic in the near future.”
Studying Ovarian Cancer in Real Time
Penn’s tissue-banking efforts are different from many others, because the tumors are living.
“Essentially, we’re collecting tissues in real time,” Dr. Drapkin said. “If you really want to answer the question, ‘How do you go from a disease that's initially chemo sensitive to one that is refractory [resistant to treatment]?’ you have to study it to the end. Unfortunately, that means until the time of death.”
The Penn Legacy Tissue Program, the first of its kind at Penn, allows ovarian cancer patients to donate their tumor tissue at the time of death to aid in research that can potentially help future ovarian cancer patients.
“The goal of the legacy program is to help us understand what we call the heterogeneity of ovarian cancer,” Dr. Simpkins said, explaining that the disease can be different in each patient, as opposed to a homogeneous condition, where the disease is similar in each patient. “It offers patients a way of giving back and a possible way of advancing the understanding of the biology of ovarian cancer so we can help women in the future.”
Ways to Give
To support ovarian cancer research at Penn, visit giving.apps.upenn.edu and choose the Ovarian Cancer Research Center Fund or call the Office of Development and Alumni Relations at 215-898-5164.