Related Experiment Video
Updated: Jan 8, 2026
Live Imaging of Microtubule Dynamics in Glioblastoma Cells Invading the Zebrafish Brain
Published on: July 29, 2022
Glioblastoma zebrafish Avatars guide therapeutic decisions in a patient with gliosarcoma: a case report
Márcia Fontes1, Daniela Garcez2, Joana Ruivo3
1Champalimaud Centre for the Unknown, Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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).
Insights
Patient-derived zebrafish xenografts (zAvatars) successfully predicted effective glioblastoma treatments. This personalized approach guided therapy selection, improving patient outcomes and offering hope for future cancer care.
Area of Science:
- Neuro-oncology
- Personalized Medicine
- Xenotransplantation Models
Background:
- Glioblastoma is an aggressive brain tumor with limited treatment options upon recurrence.
- Current clinical decisions lack functional tests, leading to suboptimal patient care and toxicity.
- There is an unmet need for personalized therapeutic strategies in recurrent glioblastoma.
Purpose of the Study:
- To evaluate the utility of patient-derived zebrafish xenografts (zAvatars) for personalized glioblastoma treatment.
- To identify effective therapeutic strategies for a patient with recurrent glioblastoma and no actionable mutations.
- To assess the predictive value of zAvatars in guiding clinical treatment decisions.
Main Methods:
- Generated patient-derived zebrafish xenografts (zAvatars) from glioblastoma tumor samples.
- Tested 13 potential off-label drug combinations in combination with radiotherapy using zAvatars.
- Sequenced tumor DNA to identify actionable mutations, which were absent in this case.
Main Results:
- Zebrafish avatars accurately predicted that Pemetrexed, alone or with Doxorubicin and Radiotherapy, induced apoptosis.
- The chosen treatment of radiotherapy with Pemetrexed, followed by Doxorubicin, resulted in patient recovery and stability.
- The patient's clinical response was consistent with the predictions made by the zAvatar model.
Conclusions:
- Rapid establishment of glioblastoma zAvatars enables timely testing of drug combinations for personalized treatment.
- Integrating tumor sequencing and zAvatar testing may enhance the management of glioblastoma patients.
- This personalized approach has the potential to improve progression-free survival (PFS) and overall survival (OS).
