A team of researchers from Brown University Health and Brown University has uncovered an important clue in the fight against glioblastoma, the most common and aggressive form of brain cancer in adults.
The team studied a rare group of patients known as ‘exceptional responders’, whose tumors are exquisitely sensitive to therapy, allowing these patients to live well beyond expectation. Through this study, Brown University Health researchers identified a powerful molecule that may pave the way for a new class of highly effective therapies.
The findings, published in the March issue of iScience , center on a molecule called miR-181d. Researchers found that tumors in these ‘exceptional responders’ contain higher levels of miR-181d, which appear to play two very important roles: weakening the tumor while also helping the body’s immune system fight back.
Typically, treatments like radiation and chemotherapy work by damaging a tumor’s DNA. But many glioblastoma cells can repair that damage, allowing the cancer to regrow. The researchers discovered that miR-181d blocks a key protein, called RAD51, that cancer cells rely on for this repair process. Without it, the tumor becomes more vulnerable to treatment.
“By studying hundreds of patient tumor samples, we found that people whose tumors have lower RAD51 levels live longer. What makes this discovery so powerful is that miR-181d naturally lowers RAD51 levels,” said Jay Hou, assistant professor of neurosurgery at Brown University Health and a key collaborator on the study. “So, miR‑181d could help make glioblastoma tumors more sensitive to treatment.”
miR‑181d provides a second important benefit to glioblastoma patients. The research also showed that miR-181d may help “switch on” the immune system against the tumor. In pre-clinical models, adding miR-181d back into tumors before radiation not only helped shrink them but also appeared to train the immune system to recognize and attack glioblastoma cells in the future.
This kind of response, in which the immune system continues to attack cancer long after treatment ends, is rare, but researchers say miR‑181d may increase the likelihood. Because long‑term survival in cancer often depends on how powerfully the immune system can stay engaged, this effect is crucial.
“We’ve been studying exceptional responders and miR-181d for more than a decade. We understand now that miR-181d sits at the very center of how glioblastomas respond to therapy and the body’s ability to mount an effective immune response against glioblastoma,” said senior author Clark Chen, MD, PhD, professor and director of the Brain Tumor Program at Brown University Health . “Our findings suggest that treating glioblastoma with miR‑181d could improve the chances that all patients live longer, much like the ‘exceptional responders’ who far outlive what this disease typically allows.”
Researchers are now working toward a clinical trial in which miR‑181d would be delivered directly into tumors during surgery to help the body mount a stronger, longer‑lasting defense against glioblastoma.
The study was a collaborative effort involving scientists from Brown University Health, Brown University, the University of Minnesota, the International Institute of Information Technology, and Johns Hopkins University.
The study can be found at :
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*Co-authors of this study also include Gatikrushna Singh, Shilpi Singh, Haoyi Zheng, Iteeshree Mohapatra, Stefan Kim, Mayur Sharma, University of Minnesota; Debashins Barik, Center for Computational Natural Science and Bioinformatics, International Institute of Information Technology; Efrosini Kokkoli, Johns Hopkins University; Sean Lawler, Shobha Vasudevan; Brown University; Jay Hou, Andrew Ni, Eric Wong, Sasmit Sarangi, Heinrich Elinzano, Margot Martinez Moreno, Sean E. Lawler, Wafik S. El-Deiry, Ziya Gokaslan, Brown University Health.
About Brown University Health :
Formed in 1994, Brown University Health is a not-for-profit health system based in Providence, R.I. comprised of three teaching hospitals of The Warren Alpert Medical School of Brown University: Rhode Island Hospital and its Hasbro Children’s Hospital ; The Miriam Hospital ; and Bradley Hospital , the nation’s first psychiatric hospital for children. They system also includes Newport Hospital , Saint Anne’s Hospital , and Morton Hospital offering a broad range of health services; Gateway Healthcare , the state’s largest provider of community behavioral health care; Brown Health Medical Group , the largest multi-specialty practice in Rhode Island; and Brown Health Medical Group Primary Care , a primary care driven medical practice. Brown University Health teaching hospitals are among the country’s top recipients of research funding from the National Institutes of Health. The hospitals received over $145 million in external research funding in fiscal 2023. All Brown University Health-affiliated partners are charitable organizations that depend on support from the community to provide programs and services.
iScience
Experimental study
Animals
miR-181d coordinates homologous recombination and anti-tumor immune responses in glioblastoma
20-Mar-2026