ChristianaCare and The Wistar Institute Advance Partnership With New Cancer Research Strategies

ChristianaCare’s Helen F. Graham Cancer Center & Research Institute is advancing its historic partnership with the Ellen and Ronald Caplan Cancer Center of The Wistar Institute in Philadelphia, Pennsylvania, with three new research projects under way.

The new research projects consist of a population health study targeting triple negative breast cancer. Other projects focus on a new therapeutic target for epithelial ovarian cancer, the most lethal gynecologic cancer in the developed world, and the development of “mini organs” derived from stem cells.

Targeting triple negative breast cancer

Delaware has one of the highest incidence rates of triple-negative breast cancer in the United States. This highly aggressive cancer has few treatment options, because the cells test negative for three known treatment targets – estrogen, progesterone and HER2 protein receptors.

Working with patient data from the Graham Cancer Center, researchers are investigating potential contributing factors such as diet, alcohol use and genetic variants among women, and the effects of these on cancer metabolism. The team will also examine spatial relationships between cancer “hot spots” — geographic areas with a higher-than-expected prevalence — and modifiable risk factors.

Key resources for the study are blood and tissue samples from the Graham Cancer Center’s Tissue Procurement Center and its statewide High-Risk Family Cancer Registry.

The research team will be led by Director of Population Health Research at ChristianaCare Scott Siegel, Ph.D., and Lead Research Scientist Jennifer Sims Mourtada, Ph.D., at the Graham Cancer Center’s Cawley Center for Translational Cancer Research (CTCR). They will join Zachary Schug, Ph.D., at Wistar’s Molecular and Cellular Oncogenesis Program.

Researching novel therapy for ovarian cancer

The latest study supported by the Graham Cancer Center’s Tissue Procurement Program targets KAT6A expression as a novel therapy for ovarian cancer caused by a specific genetic mutation, called PP2R1A.

Epithelial ovarian cancer is the most common form of ovarian cancer and the leading cause of gynecologic cancer deaths in the United States.

Chemoresistance to currently available platinum-based drugs like cisplatin represents a major treatment challenge, as more than 50 percent of affected women ultimately relapse and die from this disease.

Wistar’s Rugang Zhang, Ph.D., leader of the Immunology, Microenvironment and Metastases Program, is focused on developing novel therapeutics for subtypes of ovarian cancer that currently have no effective therapies and on improving the current standard of care.

Dr. Zhang’s previous work suggests that KAT6A signaling plays a critical role in ovarian cancer progression. Targeting this signaling pathway could be an effective strategy for treating ovarian cancer.

Working with Dr. Zhang on this project are Graham Cancer Center gynecologic oncologists Mark Cadungog, M.D., director of Robotic Surgery, and Sudeshna Chatterjee-Paer, M.D., and Cawley CTCR’s Stephanie Jean, M.D., director of Gynecologic Oncology Research. Also collaborating with the team is Wistar’s Alessandro Gardini, Ph.D., assistant professor in the Gene Expression & Regulation Program.

‘Mini organs’ offer hope for therapeutics

Dr. Sims-Mourtada at the Cawley CTCR will lead a new program to culture organ-specific tissue from stem cells that could change the way diseases are studied and treated.

These so called “mini organs” or “organoids” are three-dimensional tissue cultures grown in the lab that replicate the complexity and functions of a specific tissue or organ found in the body.

Organoids offer scientists a better model for how drugs and other therapeutics might interact with a patient’s particular type of tumor, opening new avenues for precision medicine.

“The ability to grow each patient’s tumor in a three-dimensional organoid along with our capability to create patient-derived xenograft or animal models as part of our PDX core, will allow us to fully capture the effects of genetic as well as gene altering behavioral and environmental influences that are lacking in current research models,” said Dr. Sims-Mourtada.

“Our collaboration with Wistar to build these programs raises our clinical platform to the next level for studying new cancer biomarkers and treatments.”

Advancing a pioneering partnership

The Graham Cancer Center made history when it signed a first-of-its-kind agreement in 2011 with The Wistar Institute, pairing a National Cancer Institute, NCI-designated basic research institution with a community cancer center that is also an NCI Community Oncology Research Program (NCORP).

“Our partnership with Wistar has attracted national recognition as a model of collaboration that leverages cutting-edge research to benefit cancer prevention and therapy statewide,” says Nicholas J. Petrelli, M.D., Bank of America endowed medical director of ChristianaCare’s Helen F. Graham Cancer Center and Research Institute.

“With Wistar, our productive collaborations over the last decade continue to drive discovery research toward clinical trials to benefit patients here at the Graham Cancer Center and in communities everywhere.”

The Graham Center has been “an ideal partner in our mission,” said Dario C. Altieri, M.D., Wistar president and CEO and director of the Ellen and Ronald Caplan Cancer Center. “Our scientists at Wistar have access to clinically-annotated primary patient specimens of the highest quality.

“As the majority of patients at the Graham Cancer Center are treatment naïve, this collaboration affords an opportunity to conduct unique, high impact mechanistic and correlative studies that will ultimately advance important scientific discoveries that hopefully will lead to better cancer therapies.”