Research and Philanthropy Combine to Find Potential New Target for Endometrial Cancers

James S. Duncan, PhD, associate professor in the Cancer Signaling and Epigenetics research program at Fox Chase.
James S. Duncan, PhD, associate professor in the Cancer Signaling and Epigenetics research program at Fox Chase.

PHILADELPHIA (October 23, 2020) – Researchers at Fox Chase Cancer Center have discovered a potential new target in the treatment of endometrial carcinoma, thanks in part to generous funding from Peggy’s Pathway for Women’s Cancer Care. The research was published recently in Molecular & Cellular Proteomics.

Using a technology called multiplexed inhibitor beads and mass spectrometry, James S. Duncan, PhD, associate professor in the Cancer Signaling and Epigenetics research program at Fox Chase, and colleagues profiled the kinome of endometrial tumors and normal endometrial tissues and identified a network of kinases that were overexpressed, including serine/arginine-rich splicing factor kinase 1 (SRPK1).

“This project really sums up the concept of a lot of the work that Fox Chase is trying to do when it comes to research,” Duncan said. “Peggy’s Pathway selected our project for funding because they thought our approach of looking at kinase signaling looked interesting, and, as a result, we have found something that may be actionable.”

Peggy’s Pathway for Women’s Cancer Care is a charity started in honor of Peggy Pettinato, who passed away from serous endometrial carcinoma. The organization’s mission is to raise funds for research into innovative treatments and early detection of endometrial cancer, the most common gynecologic malignancy in the United States.

According to Duncan, endometrial tumors frequently have alterations in protein kinases, a family of about 535 enzymes that are collectively termed the kinome. Kinases are altered in about one-quarter of all cancers and are considered highly susceptible to treatment with drugs because of their catalytic activity. However, only a small fraction of the kinome has been explored therapeutically.

Multiplexed inhibitor beads and mass spectrometry is a chemical proteomic strategy that allows researchers to simultaneously look at kinase levels in cells and tumors.

“From a cancer standpoint we can identify protein kinases that are up- or downregulated in cancer,” Duncan said. “Ones that are upregulated are of interest because protein kinases play a role in cancer growth, survival, and metastasis, so they often represent potential targets.”

The analysis showed that SRPK1 was overexpressed in endometrial cancer tissues and that this overexpression was associated with poor survival, suggesting that SRPK1 could be involved in key tumor-associated properties, Duncan said.

“We also discovered that in combination with therapy targeting growth factors—in this case EGFR—targeting this kinase produced strong drug synergy to kill these tumors,” Duncan said. This synergy was found for endometrioid cell lines and uterine serous cancer cell lines, a disease subtype with poor outcomes.

To further explore the role of SRPK1, Duncan and colleagues want to apply proteomic technology to try to understand more about how SRPK1 works and conduct experiments to see if EGFR and SRPK1 inhibition has an effect on endometrial cancer tumor models.

Peggy’s Pathway now has the goal of raising at least $200,000 over the next two years to fund some of this additional research at Fox Chase.

The paper, “Kinome Profiling of Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 As Candidate Therapeutic Target,” was published in Molecular & Cellular Proteomics.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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