6.5 million Americans over age 65 have a severe visual impairment. Martha Burger might have been one of them. Fortunately, she saw an eye doctor regularly and he caught a problem Martha hadn’t even noticed – one that threatened her eyesight.
It’s not unusual for a child to struggle from time to time in school, but one Oklahoma mom noticed her 11-year-old’s grades had suddenly taken a tailspin and the struggle was not with intellect or ability to learn. It turns out Jonathan couldn’t see the lessons being taught.
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.
ABOUT THE STEPHENSON CANCER CENTER
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.