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Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome
Daniel A P Guerra1, Ana E Paiva1, Isadora F G Sena1
1Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Abstract:
Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.
Insights
Targeting glioblastoma-derived pericytes with ibrutinib improves chemotherapy effectiveness and survival by enhancing blood-brain barrier permeability. This study highlights pericytes as a novel therapeutic target in malignant brain tumors.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Pharmacology
Background:
- Glioblastoma is a deadly brain cancer with limited treatment options due to the blood-brain barrier.
- Developing effective glioblastoma therapies is challenging because drug delivery to the brain is restricted.
Purpose of the Study:
- To identify novel therapeutic targets within the glioblastoma microenvironment.
- To evaluate the role of pericytes in glioblastoma progression and treatment response.
Main Methods:
- Utilized advanced technologies, including thymidine kinase targeting systems.
- Employed glioblastoma xenograft mouse models for in vivo studies.
- Investigated the effects of ibrutinib on pericytes and blood-brain barrier permeability.
Main Results:
- Targeting glioblastoma-derived pericytes significantly improved chemotherapy efficiency.
- Ibrutinib treatment demonstrated enhanced chemotherapeutic effectiveness.
- Ibrutinib treatment improved blood-brain barrier permeability and prolonged animal survival.
Conclusions:
- Glioblastoma-derived pericytes represent a novel therapeutic target in the brain tumor microenvironment.
- Ibrutinib shows promise in enhancing glioblastoma treatment by targeting pericytes and improving drug delivery.
- Further research into pericyte-targeted therapies could lead to improved outcomes for glioblastoma patients.
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