The University of North Carolina Lineberger Comprehensive Cancer Center have been experimenting for a long time with cancer treatments and drug testing to curb tumor growth. In an interesting turn of events, a team of researchers at the UNC cancer center discovered a cell signal that caused haphazard tumor growth in the advanced stages of blood cancer.
A report based on the findings from the research was posted in the Proceedings of the National Academy of Sciences Journal. The research has successfully singled out the hyperactive signal and the biological target that is directly affected by the human herpesvirus-8 (HHV-8).
During the research, the team has successfully stimulated the biological target through external medication and this could be the breakthrough required in getting an easy treatment for the primary effusion lymphoma.
Dr. Blossom Damania at the UNC Lineberger Cancer Center said, “We found a protein called Tyro3 that’s highly upregulated and expressed in a subtype of non-Hodgkin lymphoma, called primary effusion lymphoma,”.
Ms. Damania is one of the world’s most renowned virologists and serves as the Vice Dean for Research in the UNC School of Medicine, Boshamer Distinguished Professor of Microbiology and Immunology, and co-director of the UNC Lineberger virology and global oncology programs. She added, “We also developed a compound that targeted Tyro3, and we found that it killed primary effusion lymphoma cells and tumors.”
The disease under study, primary effusion lymphoma, causes uncontrolled growth and multiplication of white blood cells and further aggravates blood cancer.
“Patients with primary effusion lymphoma have a poor prognosis with a median survival time of approximately six months post-diagnosis,” said Jason Wong, a graduate student in the UNC School of Medicine Department of Microbiology and Immunology. Jason worked under Dr.Damania and was on the team that conducted the research. He added, “Since current treatment options can be ineffective, finding new therapeutic targets is a high priority.
The research aimed at finding cell signals that were particularly amped in primary effusion lymphoma. These signals, a.k.a. kinases were the culprit. As they ‘instructed’ the cells to multiply uncontrollably.
The team worked closely with Ph.D. Doctor Gary Johnson, also from the UCN Center. Mr. Johnson is also a serving as a Professor at the UNC School of Medicine. Johnson helped the team in characterizing and analyzing the activity of the cell signals in the cancerous blood cells.
Their findings showed that a cell signal named Tyro3 kinase was specifically hyperactive in primary effusion lymphoma cells. When compared with other normal cells that particular kinase did not appear hyperactive. Tyro3 kinase could prolong a cancer cell’s life.
After signaling out the culprit the team experimented with a therapeutic which they developed during the research. When the drug, UNC3810A, was administered a dose-dependent reaction of cell death and suppression of tumor growth was witnessed.
The complex compound UNC3810A was developed in-house at the UNC laboratory by Dr. Xiaodong Wang, Associate Professor (research) at the Eshelman School of Pharmacy located inside the University of North Carolina. Dr. Wang is also the medicinal chemistry director of the UNC Center for Integrative Chemical Biology and Drug Discovery.
“UNC3810A was used as an in vivo tool compound to understand the biological roles of Tyro3 in primary effusion lymphoma in this study,” Wang said. “The work towards optimizing UNC3810A to a preclinical candidate will be continued in my lab.”
“We identified a new target in a subtype of non-Hodgkin lymphoma, and this target is also upregulated in other types of cancers besides lymphomas, and so potentially the drug we developed can be used for multiple cancers,” Damania said.
The research has paved way for curing multiple cancers where the said kinase might be involved and the researchers are positive that signaling out the cell signal will help them in better understanding other cancer-related issues as well.