Shared Origins of Brain Tumors Offer New Therapeutic Targets

MEMPHIS, Tenn. – March 5, 2026 – Scientists have uncovered shared molecular dependencies across several types of brain tumors, potentially opening doors to new, broadly effective treatments. Research published today in Cancer Cell details the origins of pineoblastoma, a rare pediatric brain tumor, and reveals surprising connections to medulloblastoma and retinoblastoma.

Researchers at St. Jude Children’s Research Hospital, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and Uppsala University assembled and analyzed the largest cohort of pineoblastoma tumors to date, using single-cell resolution technology. Their work identified a critical role for light-sensing-related genes in the formation of pineoblastoma within the developing pineal gland.

Uncovering the Roots of Pineoblastoma

Pineoblastoma is a rare tumor, with St. Jude treating only a handful of cases each year, according to Paul Northcott, PhD, corresponding and co-senior author of the study and director of the St. Jude Center of Excellence in Neuro-Oncology Sciences (CENOS). “By collaborating with other institutions, we went much deeper than previous profiling efforts to understand where these tumors approach from, how they overlap or differ at single-cell resolution, and what makes them vulnerable,” Northcott said.

The research team first created a single-cell atlas of normal pineal gland development to understand the process of healthy cell formation. By comparing gene expression patterns in this atlas to those found in 38 pineoblastoma tumor samples, they pinpointed pinealocyte progenitors – early cells in the pineal gland’s development – as being most similar to the tumors. This finding implicated these progenitors in the development of pineoblastoma.

A Common Thread Across Brain Tumors

Further investigation revealed a recurring theme: the expression of light-sensing genes. The pineal gland normally expresses genes related to light sensitivity, as it plays a role in circadian rhythm and interpreting light from the retina. Researchers found these same genes were highly expressed in pineoblastoma cells, suggesting a potential “addiction” to these genes for tumor survival.

Intriguingly, this light-sensing signature wasn’t unique to pineoblastoma. The team discovered a similar pattern in Group 3 medulloblastoma and, extending their analysis, found the same genes, transcription factors, and biomarkers present in other central nervous system tumor types, including those of the retina and cerebellum.

Shared Vulnerability and Therapeutic Potential

To test the importance of these shared genes, researchers used CRISPR technology to remove them from pineoblastoma, medulloblastoma, and retinoblastoma cells. They found that all three cancer types were dependent on these genes, and tumor growth was halted when they were removed.

“We found a subset of these light-sensing genes to be very strong selective dependencies in these particular cancer types,” Northcott explained. “With that information, we’ve opened the door to explore therapeutically targeting this shared signature across multiple brain tumor types in the future.”

Study Details

The study’s co-first authors are Brian Gudenas, Anthony Liu, and Shiekh Tanveer Ahmad, of St. Jude. Bernhard Englinger, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center; and Miao Zhao, Uppsala University. Additional authors include researchers from St. Jude, Uppsala University, Harvard Medical School, Hopp Children’s Cancer Center Heidelberg (KiTZ), Medical University Vienna, University of Southern California, and Boston Children’s Hospital.

The research was supported by grants from The Mark Foundation, St. Baldrick’s Foundation, the National Cancer Institute, the Andruzzi Foundation, Alex’s Lemonade Stand Foundation, John W. And Pamela A. Cuming, Solving Kids’ Cancer, Inc./The Bibi Fund, the Burroughs Wellcome Fund, the Sontag Foundation, the Erwin Schrödinger Fellowship of the Austrian Science Fund, the Swedish Research Council, the Swedish Cancer Society, the Swedish Childhood Cancer Fund, the Swedish Brain Fund, the Li Shu Pui Medical Foundation Training Grant, the Lin Kin Pang-HKU Foundation Scholarship, and the American Lebanese Syrian Associated Charities (ALSAC).

Source: St. Jude Children’s Research Hospital