Funding Research, Fueling Hope

Founded in 1996, the Four Diamonds Pediatric Cancer Research Center is making discoveries to save the lives of children with cancer.

Thanks to the funds raised at Penn State THON to benefit Four Diamonds, more than 80 doctors and scientists at Penn State College of Medicine are able to conduct a full spectrum of cancer research, provide leading-edge therapies through a range of clinical trials, and play an important role in the advancement of pediatric cancer treatment and cure rates through participation in national and international consortia. Collectively, their efforts are focused on providing superior care to patients at Penn State Children’s Hospital, while contributing to the global pursuit of a cure for childhood cancer.

Dr. Barbara Miller, division chief, pediatric oncology and hematology and director of the Four Diamonds Pediatric Cancer Research Center, says the support from Four Diamonds has helped in continually expanding their research program.

“We conduct laboratory-based research to better understand disease mechanisms in pediatric cancer and to identify potential targets in the molecular disease process to which new drugs can be directed,” says Dr. Miller.

The need for research dedicated solely to childhood cancer is great. According to the American Cancer Society and the American Childhood Cancer Organization, an estimated 16,000 children in the United States are diagnosed with cancer each year —that’s about forty-three children every day. While childhood cancer survival rates have significantly improved to eighty percent over the past forty years, one in five children will still die from their disease within five years of diagnosis.

“I think about my age and how long I have been doing this, and frankly I’m just so tired of going in and telling families there’s nothing more we can do for their child,” says Dr. Valerie Brown, who is the director of the Experimental Therapeutics Program in the division of pediatric oncology/hematology at Penn State Children’s Hospital.

A portrait of Valerie Brown

Valerie Brown, MD, PhD

Through funding from Four Diamonds, Dr. Valerie Brown has built the Experimental Therapeutics Research and Clinical Team (ExTRaCT), a team of physicians, pharmacists, and nurses within the division of hematology/oncology that works to identify and expedite screening of potential patients for participation in early phase clinical trials.

IMAGE: Penn State

"Four Diamonds and THON allow us to offer novel therapeutic treatment options that patients would otherwise not have.” —Dr. Valerie Brown, director of the Experimental Therapeutics Program in the division of pediatric oncology/hematology at Penn State Children’s Hospital

Through funding from Four Diamonds, Dr. Brown’s position as director of the Experimental Therapeutics Program allows her not only the time, but also the resources necessary to garner national recognition for Penn State College of Medicine pediatric cancer research through participation in various nationwide consortia— groups of institutions in either a region or country and across the globe that come together with the same end goal. Working with these organizations gives patients access to new drugs and novel therapeutic approaches for cancers which are difficult to treat.

Investigators at the Four Diamonds Pediatric Cancer Research Center are members of the Children’s Oncology Group, Pediatric Oncology Experimental Therapeutics Investigators Consortium, and the Beat Childhood Cancer Consortium (formerly the Neuroblastoma and Medulloblastoma Translational Research Consortium).

“Participation in these consortia allow us to test innovative and novel approaches in a way that is more efficient while minimizing risk to the patient,” says Dr. Brown. “They act as pipelines for the next generation of studies and the catalyst for a new approach becoming the standard in care after receiving the appropriate regulatory approval.”

Investing in Research, Improving Care

For Dr. Brown, success is often seen in the unexpected side of her work. Since arriving at Penn State Children’s Hospital in 2013, she has built a team of physicians, pharmacists, and nurses within the division of hematology/oncology that works to identify and expedite screening of potential patients for participation in early phase clinical trials. Known as the Experimental Therapeutics Research and Clinical Team (ExTRaCT), the team works within a shared-care framework, which allows patients of Penn State Children’s Hospital and beyond to benefit from getting access to early phase clinical trials.

“Clinical trials are very time intensive,” says Dr. Brown. “There is a lot to be considered in terms of the clinical and regulatory standards that must be reached. Because we have a team dedicated to working diligently on these trials, when patients enroll here, not only are they getting superb care, they are being monitored and reported on appropriately.”

The diligence with which the group works has been recognized as outstanding among a number of consortia, so much so that team members have been asked to advise other groups doing this type of work.

“Identifying a group of attending physicians with varying areas of expertise has made us somewhat of a ‘go-to’ in terms of choosing what protocols will open here,” says Dr. Brown. “We keep a portfolio of trials open because not all patients meet the same criteria. We focus on diversity and depth because a lot goes into the timing to get patients enrolled.”

It’s this behind-the-scenes work that makes funding from Four Diamonds so critical.

“Four Diamonds allows me to do things like go to a consortium meeting where we generate new clinical trial protocols and then hammer out all the details,” says Dr. Brown. “It’s intensive work. But because we’re not caught up in writing so many grants to get funding, it allows us to think more directly about how we’re going to affect a patient’s outcome. Four Diamonds and THON allow us to offer novel therapeutic treatment options that patients would otherwise not have.”

Making the Impossible Possible

For Dr. Sinisa Dovat, director of Translational Research in the Pediatric Experimental Therapeutics Program, being able to apply new concepts to standard treatments has led to exciting discoveries in novel treatments for pediatric cancers like leukemia.

Dr. Dovat, who also holds professorships in the Department of Pediatrics, Department of Biochemistry and Molecular Biology, and the Department of Pharmacology, credits Four Diamonds and THON for his decision to join the Penn State College of Medicine.

“Dr. Miller had been following my work and invited me to visit,” recalls Dr. Dovat. “She was smart enough to show me the video of THON. It was something I had never ever seen in my life. I thought to myself, ‘this is something really special.’”

The focus of Dr. Dovat’s internationally-recognized laboratory is to discover how abnormities in certain genes result in cancer.

Male physician pipetting in a lab

Sinisa Dovat, PhD, MD

Dr. Sinisa Dovat's work has led to exciting discoveries in novel treatments for pediatric cancers like leukemia.

IMAGE: Penn State

“She was smart enough to show me the video of THON. It was something I had never ever seen in my life. I thought to myself, ‘this is something really special.’” —Dr. Sinisa Dovat, director of Translational Research in the Pediatric Experimental Therapeutics Program

“We are spanning two areas,” says Dr. Dovat. “Molecular mechanisms of malignant diseases like cancer—what makes cancer, what makes it progress, what makes cell multiply. The other area of focus is the discovery and design of novel drugs, which can then be taken to the clinical level.”

One of the projects he studies involves a gene called Ikaros, which is important in leukemia because it controls a number of other genes. When it is absent in patients’ cells, high-risk childhood leukemia can develop, which has a poor outcome.

“During a human’s life, sometimes mistakes happen in our genetics,” says Dr. Dovat. “Cells can lose one copy of Ikaros, and if that happens you develop really bad leukemia that is resistant to treatment. Efforts have been made to develop strong treatment options to fight it, but they are not always successful.”

One of Dovat’s published studies involves a drug that can restore the function of Ikaros and effectively suppress leukemia. The study, which has undergone rigorous testing, has been published by top journals and has received additional funding from the National Institutes of Health (NIH) and the National Cancer Institute.

“The whole idea is thinking dramatically,” says Dr. Dovat. “We think about the impossible, then make this seemingly ‘impossible’ very real, very possible, and really useful.”

For all of the physicians and researchers within the Four Diamonds Pediatric Cancer Research Center, the brink of discovery remains centered on one thing: patient outcomes.

“These kids want a cure and this is what we’re working on,” says Dr. Dovat. “And that is my primary allegiance; to them and to THON.”