Sylvester Comprehensive Cancer Center Scientists Uncover How Brain Tumors Change When They Return
An international study of tumors collected before and after recurrence found that two related forms of IDH-mutant glioma evolve through different genetic changes, offering researchers a clearer road map for future treatment strategies.
Key Takeaways
- An international team of researchers, including scientist Antonio Iavarone, M.D., deputy director of Sylvester Comprehensive Cancer Center, has uncovered distinct ways in which two types of brain cancer evolve as they recur.
- Recurrent IDH-mutant gliomas may be genetically different from the tumors first diagnosed.
- Oligodendrogliomas tended to develop new changes in individual genes associated with tumor growth.
- Astrocytomas were more likely to gain or lose large sections of chromosomes.
- Temozolomide appeared to leave distinct genetic fingerprints in some recurrent tumors.
A brain tumor that returns after treatment may be genetically different from the cancer first diagnosed.
An international team of researchers, including scientist Antonio Iavarone, M.D., deputy director of Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and director of Sylvester Brain Tumor Institute, has uncovered distinct ways in which two types of brain cancer evolve as they recur.
Published in Nature, the findings could help scientists better understand why these cancers become resistant to treatment and identify opportunities for more personalized therapies.
The research focused on IDH-mutant gliomas, brain tumors defined by mutations in isocitrate dehydrogenase, or IDH, genes. Although patients can live for years after diagnosis, these tumors almost always recur and eventually can stop responding to treatment.
“Cancer is not a static disease. A tumor continues to evolve under the pressure of treatment. Understanding those changes gives us an opportunity to think differently about how we might treat the disease when it returns,” said Dr. Iavarone, a professor of neurological surgery and biochemistry and molecular biology at the Miller School.
Following Cancer as it Changes
Understanding that evolution has been difficult because IDH-mutant gliomas are rare and researchers need samples collected from the same patients at different stages of their disease.
The international Glioma Longitudinal Analysis, or GLASS Consortium, made that comparison possible. Researchers studied tumors from 183 patients, sampled before and after recurrence, analyzing specimens collected from more than 500 surgeries across North America, Europe, Asia, Australia and South America.
That allowed scientists to examine how the tumors changed over time.
The team focused on two types of IDH-mutant glioma: astrocytoma and oligodendroglioma. Although both share the defining IDH mutation, researchers found that they followed distinctly different genetic paths as they progressed.
Oligodendrogliomas tended to develop new changes in individual genes that help tumors grow. Astrocytomas were more likely to gain or lose large sections of chromosomes, the structures that carry DNA. Some of these large-scale changes were linked to poorer outcomes after the tumors returned.
The Fingerprint of Treatment
Researchers also found evidence that treatment can influence tumor evolution.
Temozolomide, a chemotherapy drug used to treat gliomas, appeared to leave distinct genetic fingerprints in recurrent tumors. This gives researchers another window into how therapies may shape cancers as they recur.
“The long-term goal is to understand the paths these tumors are likely to take so that we can begin developing strategies designed to anticipate resistance, rather than simply reacting after a cancer has progressed,” Dr. Iavarone said.
Two Tumor Types, Different Paths
Oligodendroglioma
These tumors tended to develop new changes in individual genes that help tumors grow.
Astrocytoma
These tumors were more likely to gain or lose large sections of chromosomes. Some of these changes were associated with poorer outcomes after recurrence.
A Road Map for Future Therapies
The findings do not immediately change how patients are treated. Instead, they provide researchers with a clearer map of how these tumors evolve, information that could help guide the development and selection of future therapies.
That question is increasingly important as treatment options expand. In 2024, the U.S. Food and Drug Administration approved the IDH inhibitor vorasidenib for certain patients with these tumors.
Ultimately, the research advances a more dynamic approach to precision medicine, including understanding cancer by what a tumor looks like at diagnosis and by how it changes in response to treatment. For researchers trying to outmaneuver treatment-resistant cancer, knowing where a tumor may go next could be an important step toward staying ahead of it.
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Tags: biochemistry and molecular biology, brain cancer, brain tumors, Department of Biochemistry and Molecular Biology, Department of Neurological Surgery, Dr. Antonio Iavarone, gliomas, neurological surgery, Sylvester Brain Tumor Institute, Sylvester Comprehensive Cancer Center