Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance

• DOI: 10.1158/2767-9764.crc-23-0298
• Publication Date: 2023-11-27T13:44:20Z
• Authors: William Echavidre; Jérôme Durivault; Célia Gotorbe; Thays Blanchard; Marina Pagnuzzi; Valérie Vial; Florian Raes; Alexis Broisat; Rémy Villeneuve; Régis Amblard; Nicolas Garnier; Cécile Ortholan; Marc Faraggi; Benjamin Serrano; Vincent Picco; Christopher Monte...
• Keywords: Radioresistance

Abstract Medulloblastoma is one of the most prevalent solid tumors found in children, occurring brain's posterior fossa. The standard treatment protocol involves maximal resection surgery followed by craniospinal irradiation and chemotherapy. Despite a long-term survival rate 70%, wide disparities among patients have been observed. identification pertinent targets for both initial recurrent medulloblastoma cases imperative. Both primary are marked their aggressive infiltration into surrounding brain tissue, robust angiogenesis, resistance to radiotherapy. While significant role integrin-αvβ3 driving these characteristics has extensively documented glioblastoma, its impact context remains largely unexplored. Integrin-αvβ3 was be expressed subset with medulloblastoma. We investigated using medulloblastoma-derived cell lines β3-subunit depletion or overexpression vitro vivo settings. By generating radioresistant lines, we uncovered an increased expression, which correlated susceptibility pharmacologic inhibition cilengitide, competitive ligand mimetic. Finally, conducted single-photon emission computed tomography (SPECT)/MRI studies on orthotopic models radiolabeled (99mTc-RAFT-RGD). This innovative approach presents potential novel predictive imaging technique realm Altogether, our findings lay foundation employing SPECT/MRI identify specific eligible integrin-αvβ3–directed therapies. breakthrough offers pathway toward more targeted effective interventions Significance: study demonstrates integrin-αvβ3’s fundamental tumorigenicity radioresistance effect expression cilengitide functional activity.