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Tumor recurrence and therapeutic resistance: exploring and exploiting the post-r...

Tumor recurrence and therapeutic resistance: exploring and exploiting the post-radiotherapy brain microenvironment for therapeutic opportunities in malignant brain tumors Gliomas are the most common brain tumors and the highest-grade glioma, glioblastoma (GBM), is arguably the most aggressive tumor type, with no long-term survivors. Patients with GBM are treated with radiotherapy, chemotherapy, sur... ver más

31/08/2027

LUNDS UNIVERSITET

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

LUNDS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 1 Participantes

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-04-11

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2021-COG: ERC CONSOLIDATOR GRANTS

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Cerrada hace 3 años

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1 Participantes

LUNDS UNIVERSITET

2.00M€ | Lider

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Duración del proyecto: 64 meses Fecha Inicio: 2022-04-11
Fecha Fin: 2027-08-31

Líder del proyecto

LUNDS UNIVERSITET

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Gliomas are the most common brain tumors and the highest-grade glioma, glioblastoma (GBM), is arguably the most aggressive tumor type, with no long-term survivors. Patients with GBM are treated with radiotherapy, chemotherapy, surgery, and tumor treating fields. Despite initial response all tumors recur as incurable lesions; there is an urgent need for novel therapeutic approaches for this patient group. The majority of GBMs recur within the treatment field receiving high-dose radiotherapy during treatment of the primary tumor; the recurrent tumor thus forms in an irradiated microenvironment. Despite the fact that it is the recurrent tumor that ultimately kills the patient and that the majority of new therapeutic agents for GBM are tested clinically in the recurrent setting, the majority of experimental models and clinical materials for drug discovery are based on primary disease. Recent advances established a central role for the tumor microenvironment in determining the therapeutic response of GBM cells, and our lab demonstrated that standard of care radiotherapy of the primary tumor can shape the microenvironment to generate tumor-supportive conditions in the recurrent tumor; These findings suggest that there is untapped potential in targeting the irradiated microenvironment. This proposal aims to explore and exploit the recurrent brain tumor microenvironment by i) consolidating the contribution of the irradiated brain tumor microenvironment to GBM resistance by integrating spatial transcriptomics, single cell RNA sequencing, and multiplexed immunohistochemistry from state-of-the-art murine and human models of GBM treatment and recurrence, and ii) discovering and targeting novel therapeutic targets unique to the post-radiotherapy brain tumor microenvironment by high-throughput phenotypic screening, with the ultimate goal of exploiting reversible stromal radiation responses and leverage novel therapeutic opportunities unique to the irradiated brain.

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