Creating New Roadblocks for Ovarian Cancer

July 22, 2016

Creating New Roadblocks for Ovarian Cancer

Want to stop traffic? Throw up a roadblock.  Soon though, cars will wind their way east or west, north or south to find ways around the roadblock to reach the desired destination. It is much the same way with cancer.   

Now, though, with a new $792,000 grant from the American Cancer Society, researchers at the Stephenson Cancer Center at the University of Oklahoma and the OU College of Pharmacy hope to help build better roadblocks for ovarian cancer.

According to American Cancer Society estimates, about 22,000 women will receive a new diagnosis of ovarian cancer this year, and more than 14,000 will die from the disease.  

“It is well recognized that patients with ovarian cancer, in general, have a poor prognosis with the current standard of care. This is due, in part, to the fact that the disease often is not diagnosed until it has already reached an advanced stage,” said Principal Investigator Sukyung Woo, Ph.D., a cancer center member and assistant professor in the Department of Pharmaceutical Sciences at the OU College of Pharmacy. “Unlike other cancers where targeted therapy has been widely adopted, effective new treatments for ovarian cancer have lagged.”

Woo hopes to change that with the help of a multi-disciplinary team of experts that includes biologists, imaging experts and clinicians with extensive experience in gynecologic oncology, including Doris Benbrook, Ph.D.; Rheal Towner, Ph.D.; and Katherine Moxley, M.D. Together, they will first take aim at the ability of ovarian cancer to eventually become resistant to some of the treatments currently available.   

“Bringing one new drug to market, from the lab to the patient, can take about 10 years. So the most immediate help would be to find a better way with the same drugs, for instance, finding the most effective doses. That’s immediate,” Woo said.

She explained ovarian cancer’s ability to grow rapidly depends upon satisfying the tumor’s ever-increasing need for nourishment.  To meet this need, the tumor sends out messages that tell the body to build new supply lines to the tumor in the form of blood vessels, a process known as angiogenesis. The antiangiogenic drug currently used against ovarian cancer targets that process by blocking the most prominent pathway. It’s a bit like throwing up a “Road Closed” sign, cutting off the tumor’s blood supply to starve it out.

Unfortunately, Woo said when that happens, it does not last long, and soon the tumor sends out signals over different pathways, triggering the re-growth of blood vessels to feed the tumor.  It’s the equivalent of finding a detour, a way around the initial drug-induced “roadblock.”

One might suppose that increasing the dose of the cancer-fighting drug would make the internal “roadblock” stronger; but in fact, it appears to do just the opposite for certain drugs. 

“If the dose given to block the prominent pathway is too strong, then the tumor tries even harder to activate the other pathways to bring the blood vessels to feed it. Thus higher doses could cause the development of drug resistance more quickly than lower doses did. For antiangiogenic drugs, high doses are not necessarily the most effective. So the focus with our current standard of care needs to shift from maximum tolerated dose to the biologically optimal dose,” said Woo.

The research team is focused on determining the biologically optimal dose of current antiangiogenic drugs as well as identifying new ways to target the activation of compensatory pathways for angiogenesis.  To accomplish both, Woo and her team will evaluate tumor cell signaling along the prominent pathway and also along multiple other pathways leading to treatment resistance. 

“It’s a different approach than before because we are looking at tumor cell signaling over a time period, not just before a drug is given and after it is given. It’s a dynamic process. It’s not just one level that is constantly maintained.  It changes over time. So we follow it in a time-dependent manner when the drug is given, evaluate when it reaches maximum treatment benefit and determine how the changes are related to treatment outcomes,” Woo explained.

The team will rely on a complex system that includes laboratory analysis, complicated mathematical calculations, computational modeling and clinical validation. 

“Integrating computational modeling with circulating biomarkers to predict treatment outcomes is a novel approach and one that we believe can have a great impact on the fight to save the lives of women diagnosed with ovarian cancer,” Woo said.

Woo and fellow researchers believe it is a process that will improve the way current anti-cancer drugs are used in the fight against ovarian cancer while also identifying which alternate pathways are most promising as targets in the development of new cancer-fighting drugs and one that ultimately will save more lives.

Woo’s research is supported by a Research Scholar Grant, RSG-16-006-01-CCE, from the American Cancer Society.

Oklahoma’s only comprehensive academic cancer center, the Stephenson Cancer Center at the University of Oklahoma is a nationally noted leader in research and patient care. The Stephenson Cancer Center annually ranks among the top three cancer centers in the nation for patients participating in National Cancer Institute-sponsored treatment trials, and it is one of 30 designated lead centers nationally in the Institute’s National Clinical Trials Network. In collaboration with the Oklahoma Tobacco Settlement Endowment Trust, the Stephenson Cancer Center is decreasing the burden of cancer in Oklahoma by supporting innovative laboratory, clinical and populations-based research. The Stephenson Cancer Center has 200 research members who are conducting more than 165 cancer research projects at institutions across Oklahoma. This research is supported by $41.2 million in annual funding from the National Cancer Institute, the American Cancer Society and other sponsors.  
Building Better Roadblocks For Cancer

Friday, July 22nd, 2016

Want to stop traffic? Throw up a roadblock.  Soon though, cars will wind their way east or west, north or south to find ways around the roadblock to reach the desired destination. It is much the same way with cancer.

Oklahoma Mom Nearly Loses Eye to Fireworks Injury

July 1, 2016

Oklahoma City woman joins Dean McGee Eye Institute in issuing fireworks warning this holiday weekend

It was just a silly game, but it involved fireworks and it nearly cost one Oklahoma mom her eye.

Rebecka Rich, 26, sustained a severe eye injury during a 4th of July game in which participants fired roman candles at one another across a small pond. It has been two years since the accident, and with the help of her doctors at the Dean McGee Eye Institute, the Oklahoma City mother of three hopes her eye and possibly her vision might still be saved.

“I didn’t see it coming toward me. I could hear it, but I thought it was going to just go by me. Then when it hit, it was like looking up at a surgeon’s light,” Rich said. “I remember running and screaming, ‘My eye. My eye.’ And I rinsed it out and all I felt was huge pain.”

Rich’s husband rushed her to the nearest emergency room, which was about 40 miles away. That hospital quickly transferred Rich to the OU Medical Center in Oklahoma City where their trauma team and the eye trauma specialists from the Dean McGee Eye Institute took over her care.

rebecka-rich-eye-exam“Rebecka, unfortunately, sustained a severe injury to the eyelid, the conjunctiva and the cornea, as well as the eyelids,” said Dr. Rhea Siatkowski, a specialist at the Dean McGee Eye Institute. She also is a clinical associate professor of ophthalmology with the University of Oklahoma Health Sciences Center.

“So far , she’s undergone one surgery within the first two weeks of the injury. We actually put a membrane on the eye and sewed the eye closed to allow it to heal and the inflammation to diminish until we could start reconstruction,” Siatkowski added.

There are an estimated 11,000 injuries caused by fireworks each year. One in every five of those involves an injury to the eye.

“Probably the most common eye injury from a firework is going to be a corneal abrasion, but much more serious injuries can occur, including hemorrhages within the eye, perforation of the eyeball itself, extensive lid burns, vitreous hemorrhage, retinal detachment and even perforation of the eyes. So we can’t stress this enough. Fireworks are very dangerous and injury to the eye caused by fireworks can be blinding,” Siatkowski said.

Rich said she had heard the statistics before. She had heard the warnings too. She just never imagined that it would ever happen to her. That’s why Rich decided to share her story in hopes that it might help others understand that it can happen to anyone. The experts at the Dean McGee Eye Institute could not agree more.

“Fireworks injuries are on the rise and probably the most important recommendation regarding fireworks is to leave them to the professionals,” Siatkowski said. “Spectators should wear eye protection, especially at private displays. Bottle rockets are potentially a huge threat and injuries from those to spectators are a very real possibility.”

rebecka-rich-and-dr.-siatkowskiSiatkowski added that children never should be allowed to handle fireworks and that includes sparklers.
Rich knows that fireworks will forever be off limits for her three children.

“It has changed everything. We don’t do the normal Fourth of July activities. We don’t go watch fireworks. We stay home and if the kids want to see fireworks, we can see them from our house to downtown or watch them on TV. But we don’t go to a location where they would do it. It’s just too much of a risk,” she said.

The physical pain has been tough, but the emotional pain even tougher for Rich.

“In my eyes … in my mind … I felt like I looked so disfigured. I could now relate to how people born with deformities or who have accidents such as mine or any kind of other accident, how they feel. Because I wouldn’t wish it on my worst enemy. It was definitely devastating,” she said.

Rich faces more surgery, more pain and more healing to repair the damage done by a single errant roman candle on the Fourth of July 2014.
“Her outlook is still guarded. There’s a chance she’ll still maintain useful usage from the injured eye in the future,  but it’s likely to require multiple operations to reconstruct the surface of her eye and then replace her cornea,” Siatkowski said.
It has taken all of the strength in her to overcome the physical and emotional pain of her injuries, but Rich is not about to give up.

“It’s a long road. It’s a long fight to get back to where I was ̶ to show I am not just going to lay down. It’s made me a stronger person than I thought I ever was.”

About the Dean McGee Eye Institute
The Dean McGee Eye Institute is dedicated to serving all Oklahomans and the global community through excellence and leadership in patient care, education and vision research. It is one of the largest and most respected centers for medical and surgical eye care in the United States and houses the Department of Ophthalmology for the University of Oklahoma College of Medicine. Its research and training programs are among the most highly regarded in the country. Twenty-one of the Institute’s ophthalmologists are listed in the Best Doctors in America and/or Castle Connolly’s Top Doctors; its Director of Vision Research is a Past President of the International Society for Eye Research, Past Vice President of the Association for Research in Vision and Ophthalmology (ARVO) and a recipient of ARVO’s prestigious Proctor Medal; two members of the faculty are recent directors of the American Board of Ophthalmology; three serve or have recently served on the Board of Trustees of the American Academy of Ophthalmology (AAO); one was Vice Chair of the Residency Review Committee in Ophthalmology for the Accreditation Council for Graduate Medical Education; one is President-Elect of the AAO; and another is a Past President of the AAO and Past President of the American Glaucoma Society. For more information, visit

Oklahoma Mom Nearly Loses Eye to Fireworks Injury

Friday, July 1st, 2016 at 11:30am

It was just a silly game, but it involved fireworks and it nearly cost one Oklahoma mom her eye.

The Fight to Save an Eye

Friday, July 1st, 2016

It was just a silly game, but it involved fireworks and it nearly cost one Oklahoma mom her eye.

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