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Glioblastoma zebrafish Avatars guide therapeutic decisions in a patient with gliosarcoma: a case report

Year: 2025

Type: article

Abstract: Glioblastoma is the most common and lethal brain tumor. Therapeutic options after recurrence are scarce and with no agreement as to which treatment to offer. Also, no functional tests are currently in use to guide clinical decisions. As a result, patients often undergo multiple treatments, being exposed to toxicities and wasting valuable time. Here we report a case of a 37-year-old man with a left temporal glioblastoma (gliosarcoma subtype), who underwent several surgeries and treatments. Tumor DNA sequencing revealed no actionable mutations. At the second recurrence, brain MRI showed three new left-hemisphere nodular lesions, leading to a third surgery. However, twenty-days post-surgery the patient relapsed. Therapeutic options available for this patient were no longer well defined and 13 possible off-label options emerged. Fresh tumor samples were used to generate patient-derived zebrafish xenografts (zAvatars) to test the 13 options in combination with radiotherapy. Pemetrexed, and Pemetrexed with Doxorubicin together with Radiotherapy, were both effective in inducing apoptosis. Due to toxicity concerns, the physician opted for the combination of radiotherapy and pemetrexed, with doxorubicin introduced later. The patient recovered and was stable for two months, consistent with the zAvatar prediction. The rapid establishment of zAvatars from glioblastoma tumor samples allows for the testing of drug combinations and the tailoring of treatment in a personalized and timely manner. A future pipeline of tumor sequencing together with zAvatars testing, since the first surgery, may help manage patients more effectively, potentially improving their Progression free survival (PFS) and overall survival (OS). Glioblastoma is the most aggressive type of brain tumor, with limited treatment options and poor prognosis. We report the case of a 37-year-old man with recurrent glioblastoma. After his third surgery, the tumor rapidly recurred, and various treatment options were considered. To guide the decision, tumor cells from the patient were implanted into zebrafish embryos to create “zAvatars,” which were then treated with the 13 therapies and radiotherapy. Two treatment options resulted in more tumor killing in the zAvatars. The patient was treated according to the zAvatar-test, stabilizing the patient for two months. Our findings show that zAvatars could be used to rapidly evaluate multiple therapy options, enabling doctors to tailor treatments in a personalized manner. Fontes et al. report a case study of a person with recurrent glioblastoma for whom patient-derived zebrafish xenografts (zAvatars) were used to test 13 off-label therapies with radiotherapy. zAvatars identified pemetrexed and doxorubicin as effective, guiding treatment that stabilized the patient.

Source: Communications Medicine

DOI: 10.1038/s43856-025-01314-7