Researchers find potential new target for endometrial cancers
Researchers at Fox Chase Cancer Center have discovered a potential new target in the treatment of endometrial carcinoma' The research was published recently in Molecular & Cellular Proteomics.
Using multiplexed inhibitor beads and mass spectrometry, James S. Duncan, associate professor in the cancer biology 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, or SRPK1.
According to Duncan, endometrial tumors frequently have alterations in protein kinases, a family of about 535 enzymes 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.
"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.
![Endometrial-cancer-890x593.jpg Endometrial-cancer-890x593.jpg](/getattachment/e15d934e-1222-44a9-98e7-30bf90835ae6/Endometrial-cancer-890x593.jpg)
Enjoy reading ASBMB Today?
Become a member to receive the print edition monthly and the digital edition weekly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles
![The quest to treat and cure xerostomia](/getmedia/09045019-5c58-4434-9eb0-d6be609842cb/Xerostomia-thumb.jpg?width=480&height=270&ext=.jpg)
The quest to treat and cure xerostomia
Blake Warner, chief of the Salivary Disorders Unit at the NIH talks about his lab’s efforts to develop treatments for dry mouth.
![There's more to blue cheese than just the stench](/getmedia/65d1751a-27b4-405b-9210-8cde34249ef5/More-to-blue-cheese-480x270.jpg?width=480&height=270&ext=.jpg)
There's more to blue cheese than just the stench
Virginia Tech researchers discovered a way to synthesize a compound in the mold of blue cheese that has antibacterial and anticancer properties.
![Engineering cells to broadcast their behavior can help scientists study their inner workings](/getmedia/a5c8da38-1a39-4183-be72-85d5cbff8a29/Engeneering-cells-to-broadcast-480x270.jpg?width=480&height=270&ext=.jpg)
Engineering cells to broadcast their behavior can help scientists study their inner workings
Researchers can use waves to transmit signals from the invisible processes and dynamics underlying how cells make decisions.
![From the journals: JBC](/getmedia/a3620094-c80e-41b9-91ab-22037b087112/FTJ-JBC-07-19-24-480x270.jpg?width=480&height=270&ext=.jpg)
From the journals: JBC
Lung cancer cells resist ferroptosis. ORMDL3 in ulcerative colitis. Novel genetic variants in thyroid cancer. Read about these recent papers.
![Seeking the sweet spot to beat a pig parasite](/getmedia/30869767-881b-438b-9f19-531ef9eee79e/Pig-parasite-480x270.jpg?width=480&height=270&ext=.jpg)
Seeking the sweet spot to beat a pig parasite
Researchers extracted, separated and tested glycans from the porcine whipworm in an effort to determine the best way to develop treatments and vaccines.
![Radioactive drugs strike cancer with precision](/getmedia/f3a6418b-340a-43cc-b53f-30916dbbd8f4/Radioactive-drugs-strike-cancer-480x270.jpg?width=480&height=270&ext=.jpg)
Radioactive drugs strike cancer with precision
The tumor-seeking radiopharmaceuticals are charting a new course in oncology, with promise for targeted treatments with fewer side effects.