UCLA Journal of Radiation Oncology_SS 2025_FOR PRINT - Flipbook - Page 35
UCLA RADIATION ONCOLOGY JOURNAL
Tr e a t m e n t S t r a t e g y R e p r o g r a m s B r a i n C a n c e r C e l l s ,
H a l t i n g Tu m o r G r o w t h
UCLA scientists have identi昀椀ed a potential new strategy for treating
the combination of radiation and forskolin, a drug compound known
glioblastoma, the deadliest form of brain cancer, by reprogramming
to in昀氀uence cell di昀昀erentiation by promoting the maturation of cells
aggressive cancer cells into harmless ones.
into neurons, which do not divide uncontrollably like cancer cells.
The 昀椀ndings, published in the Proceedings of the National Academy
“Our approach is unique because it leverages the timing and e昀昀ects
of Sciences, demonstrate that combining radiation therapy with
of radiation,” said Dr. Ling He, an Assistant Project Scientist in
a plant-derived compound called forskolin can force glioblastoma
UCLA’s Department of Radiation Oncology and 昀椀rst author of
cells into a dormant state, making them incapable of dividing or
the study. “Unlike traditional therapies that force cancer cells to
spreading.
mature, we use radiation to create a temporary, 昀氀exible state, making
glioma cells easier to guide into specialized, less harmful types. By
When tested in mice, the addition of forskolin to radiation prolonged
adding forskolin at the right moment, we push these cells to become
survival, o昀昀ering a potential new avenue for combating glioblastoma,
neuron-like or microglia-like, reducing their potential to regrow into
a disease with limited treatment options and a median survival time
tumors.”
of just 15 to 18 months after diagnosis.
To test whether forskolin could reprogram these cells, the team
“Radiation therapy, while e昀昀ective in killing many cancer cells,
of scientists examined the combined treatment’s e昀昀ects on cellular
also induces a temporary state of cellular 昀氀exibility,” said Dr. Frank
behavior, including the expression of neuronal markers, cell cycle
Pajonk, Professor of Radiation Oncology at the David Ge昀昀en
distribution and proliferation. Gene expression changes were
School of Medicine at UCLA and the study’s senior author. “We
analyzed using RNA sequencing, while single-cell RNA sequencing
found a way to exploit this 昀氀exibility by using forskolin to push these
revealed how individual glioblastoma cells transitioned into new
cells into a non-dividing, neuron-like or microglia-like state.”
phenotypes. The impact on glioma stem cells was assessed through
limiting dilution assays. The approach was then tested in mouse
Glioblastoma is notoriously di昀케cult to treat, largely due to the
models to assess its ability to improve survival.
cancer cell’s ability to divide uncontrollably and the protective
blood-brain barrier that limits the e昀昀ectiveness of therapies.
The researchers found that the forskolin was able to cross the blood-
Current standard treatments—surgery followed by chemotherapy
brain barrier, signi昀椀cantly depleting glioma stem cells and slowing
and radiation—have remained unchanged for two decades. A key
tumor proliferation.
problem is the ability of glioma stem cells to regenerate tumors after
treatment and resist conventional therapies, making them a primary
This approach also signi昀椀cantly slowed tumor growth in mice
reason for treatment failure.
and, in some cases, led to long-term tumor control. In the highly
aggressive and fast-growing model, the combination therapy
Recent discoveries suggest that radiation not only kills some
extended the median survival from 34 days to 48 days. Similarly,
glioblastoma cells, but also temporarily makes the glioma stem cells
in the less aggressive glioma mouse model, the median survival
more 昀氀exible, or adaptable, providing an opportunity to alter their
increased to 129 days with the combination treatment, compared
identity.
to 43.5 days in mice treated with radiation alone. Importantly, the
sublethal radiation doses used have minimal e昀昀ects on their own,
Building on this concept, the UCLA researchers decided to look at
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