SAN ANTONIO, March 26, 2025
Research led by The University of Texas Health Science Center at San Antonio identifies a means of blocking recurrence of glioblastoma, the deadliest brain cancer.
Advertisement
SAN ANTONIO, March 26, 2025 /PRNewswire-PRWeb/ --�Researchers at The University of Texas Health Science Center at San Antonio have discovered a way to delay or even block recurrence of the deadliest brain cancer after radiation, bringing new hope for survival.
Advertisement
Ironically, the scientists found that the customary treatment for glioblastoma, ionizing radiation, can also cause tumors to recur, by generating senescent or aged cells that secrete molecules that can spur growth of neighboring cancer cells.
But they discovered that a new class of experimental "senolytic" drugs, given after radiation, can kill those senescent cells while sparing normal ones, thereby stemming recurrence. A senolytic refers to a novel class of small molecules thought to selectively induce death of senescent cells.
"These findings lend credence to the 'one-two punch' approach to radiation therapy, where radiation or other agents are first used to induce senescence in a tumor, and then the senescent cells are removed by a senolytic," said Sandeep Burma, PhD, professor and vice chair (research) of neurosurgery at UT Health San Antonio and its Mays Cancer Center.
Burma and Bipasha Mukherjee, PhD, associate professor of neurosurgery at UT Health San Antonio, are lead authors of the study, "Targeting cIAP2 in a novel senolytic strategy prevents glioblastoma recurrence after radiotherapy," published Feb. 19 in the journal EMBO Molecular Medicine. Other authors also are with the departments of neurology, biochemistry and structural biology, and medicine at UT Health San Antonio, as well as the University of Texas Southwestern Medical Center in Dallas, and the Mayo Clinic of Rochester, Minnesota.
A double-edged sword
Recurrence of glioblastoma, the most common primary brain tumor in adults, is a major clinical problem as it occurs quickly and can be even more aggressive. Accordingly, Burma's lab has focused on understanding the forces driving recurrence and strategies to block the process.
Specifically, they are trying to understand whether senescence of cancer cells after radiation therapy � also called therapy-induced senescence, or TIS � might counterintuitively be driving recurrence.
Burma said that ionizing radiation, which is routinely and, in many cases, effectively used to treat cancer, is a double-edged sword since radiation also is a powerful carcinogen. For glioblastoma, radiation is still the most effective therapy. But radiation exposure also is the only known risk factor for its development, and could perhaps also drive recurrence.
When a tumor is radiated, a cancer cell can either die or remain alive but be permanently unable to divide further, a state called senescence, with both outcomes controlling tumor growth.
However, researchers in this study discovered that senescent glioblastoma cells secrete large amounts of growth factors and other molecules that can act on persisting cancer cells and encourage them to re-proliferate. What could be done about this problem?
End of senescence
Senolytic gets its name from the words "senescence" and "lytic," or destroying.
The researchers found that senescent glioblastoma cells rely on an anti-apoptotic protein, or one that slows or prevents cell death known as cIAP2, for survival. They also found that targeting cIAP2 with a senolytic drug called birinapant in mouse tumor models after radiation could kill senescent cells while sparing normal cells.
They tested their approach in multiple mouse models of glioblastoma and found that while the drug was not effective on its own, it was very effective at delaying or even preventing recurrence if given as an "adjuvant" after radiotherapy.
"These pre-clinical results highlighting a novel senolytic approach for glioblastoma are very exciting from a clinical standpoint as they clearly indicate that significant improvement in patient survival may become possible by eliminating senescent cells arising after radiotherapy," Burma concluded.
Targeting cIAP2 in a novel senolytic strategy prevents glioblastoma recurrence after radiotherapy
Nozomi Tomimatsu, Luis Fernando Macedo Di Cristofaro, Suman Kanji, Lorena Samentar, Benjamin Russell Jordan, Ralf Kittler, Amyn A. Habib, Jair Machado Espindola-Netto, Tamara Tchkonia, James L. Kirkland, Terry C. Burns, Jann N. Sarkaria, Andrea Gilbert, John R. Floyd, Robert Hromas, Weixing Zhao, Daohong Zhou, Patrick Sung, Bipasha Mukherjee, Sandeep Burma
First published: Feb. 19, 2025, EMBO Molecular Medicine
Link to full study: https://www.embopress.org/doi/full/10.1038/s44321-025-00201-x
The University of Texas Health Science Center at San Antonio (UT Health San Antonio), a primary driver of San Antonio's $44.1 billion health care and biosciences sector, is the largest academic research institution in South Texas with an annual research portfolio of more than $436 million. Driving substantial economic impact with its six professional schools, a diverse workforce of more than 9,400, an annual expense budget of $1.67 billion and clinical practices that provide 2.5 million patient visits each year, UT Health San Antonio plans continued growth over the next five years and anticipates adding more than 1,500 higher-wage jobs to serve San Antonio, Bexar County and the South Texas region. To learn about the many ways "We make lives better�," visit The University of Texas Health Science Center at San Antonio UTHealthSA.org
Stay connected with The University of Texas Health Science Center at San Antonio on Facebook, Twitter, LinkedIn, Instagram and YouTube.
The Mays Cancer Center at UT Health San Antonio is one of only four National Cancer Institute-designated Cancer Centers in Texas. The Mays Cancer Center provides leading-edge cancer care, propels innovative cancer research and educates the next generation of leaders to end cancer in South Texas. To learn more, visit https://cancer.uthscsa.edu.
Stay connected with the Mays Cancer Center on Facebook, Twitter, LinkedIn, Instagram and YouTube.
Media Contact
Steven Lee, The University of Texas Health Science Center at San Antonio, 2104503823, lees22@uthscsa.edu, https://news.uthscsa.edu/
View original content:https://www.prweb.com/releases/ut-health-san-antonio-led-research-discovers-a-way-to-slow-or-block-recurrence-of-glioblastoma-302412494.html
SOURCE The University of Texas Health Science Center at San Antonio
