SUMMARY
The research team led by Craig M. Horbinski, M.D., Ph.D., works on a variety of translational brain tumor projects, including preclinical therapeutic testing and biomarker development. The team's work centers on two primary tumor types: meningiomas and isocitrate dehydrogenase (IDH)-mutant gliomas. One area of investigation focuses on aggressive meningiomas and evaluates a novel treatment strategy involving the local delivery of bioresorbable, chemotherapy‑infused wafers. Another project applies artificial intelligence (AI) to routine meningioma histopathology to extract more meaningful prognostic features. This approach aims to better predict tumor behavior and to identify patients who may benefit from additional molecular testing to further refine prognosis.
Dr. Horbinski's laboratory also is pursuing ongoing studies of IDH‑mutant gliomas. One project is the development of a new combination chemotherapy regimen for high‑grade IDH‑mutant gliomas that do not respond to IDH‑mutant enzyme inhibitors. Another project is the identification of molecular markers that predict responsiveness to these enzyme inhibitors.
In addition, the team collaborates with other Mayo Clinic investigators to create a methylation sequencing-based test designed to support the clinical evaluation of cancers, including brain tumors.
Focus areas
- Chemotherapy-infused bioresorbable wafers. Meningiomas tend to occur locally and only rarely spread to other parts of the body. Therefore, they may be particularly well suited for treatment strategies that deliver therapy directly to the tumor site. Dr. Horbinski and his team develop and study bioresorbable wafers infused with a combination of chemotherapies designed to target a broad range of meningiomas. The goal is for these wafers to be implanted at the neurosurgical resection site of a meningioma and to gradually release the chemotherapies, eliminating residual tumor cells before they have a chance to re-form. This also avoids the toxic effects of systemic chemotherapy delivery.
- AI‑based prognostication in meningiomas. Meningiomas are among the most diverse tumors of the human body, with 15 morphological variants recognized by the current World Health Organization classification system. Many histopathologic features are challenging to quantify reliably using traditional observer-based light microscopy. These challenges limit the prognostic power of the existing grading scheme. In contrast, a trained AI program can systematically quantify these features and more accurately predict meningioma behavior. This approach has the potential to substantially improve patient management and to better target advanced molecular diagnostics toward meningiomas most likely to harbor a high risk of genetic alterations.
- Therapeutic strategies and biomarker development in IDH‑mutant gliomas. A subset of diffusely infiltrative gliomas harbor mutations in isocitrate dehydrogenase 1 or 2, also known as IDH1 and IDH2. These mutations alter cellular metabolism and promote gliomagenesis. Although inhibitors targeting mutant IDH enzymes can delay progression in World Health Organization grade 2 IDH‑mutant gliomas, they are less effective in grade 3 and 4 tumors. To address this unmet need, Dr. Horbinski's laboratory is repurposing existing chemotherapies in combination with novel agents to treat higher grade IDH‑mutant gliomas. In parallel, the team is investigating how prolonged exposure to IDH‑mutant inhibitors alters the epigenome of these tumors. The goal of this research is to identify molecular biomarkers that predict therapeutic response.
- Methylation sequencing for cancer diagnostics. Methylation sequencing is a molecular technique that can generate the whole-genome mutation, copy number and methylation profiles of a tumor using a single test. This approach requires less biopsy material and is substantially more cost‑effective than current diagnostic methods. As a result, methylation sequencing has the potential to transform the clinical workup of cancer. Dr. Horbinski's team develops and validates this assay for routine use in cancer diagnostics, with the goal of supporting more-personalized patient management while reducing overall cost and tissue requirements.
Significance to patient care
Dr. Horbinski's research helps improve the care of patients with brain tumors. His laboratory works to develop better ways of accurately diagnosing and treating brain tumors. The team focuses primarily on meningiomas and IDH-mutant gliomas, both of which are serious tumors that need new treatment strategies. They also collaborate with other Mayo Clinic researchers to create and validate a new type of molecular test for cancer that can provide more clinically useful information at a lower cost. This test has the potential to replace many existing diagnostic tests.
Professional highlights
- Site lead, Bioresource, Mayo Clinic in Florida, 2026-present.
- Vice-chair, Translational research, Neuro-oncology Committee, Alliance for Clinical Trials in Oncology, 2026-present.
- Member, American Society for Clinical Investigation, 2024-present.
- Member, Pluto Society, American Association of University Pathologists, 2024-present.
- Contributor, Fifth and Sixth Editions, World Health Organization Classification of Tumours of the Central Nervous System, 2021, 2026.
- Contributor, Update on genetic tumor syndromes, Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, 2026.
- Top Poster Award, "Predicting Venous Thromboembolism in Patients With Adult‑Type Diffuse Gliomas," 27th Annual Meeting of the Society for Neuro‑Oncology, 2022.
- Weil Award for Best Paper on Experimental Neuropathology, "Preclinical and Clinical Characteristics of Seizures in IDH‑Mutant Gliomas," American Association of Neuropathologists Meeting, 2022.
- Tomasulo Award for Distinguished Biology Alumnus, Canisius University, 2021.