St. Jude Reference #SJ-10-0020
Dr. David Ellison, MD PhD, head of the Pathology Department at St. Jude, has designed a panel of immunohistochemical assays that can be used to identify distinct medulloblastoma molecular subgroups. Subgrouping allows more effective treatment based on newer, targeted therapies. This new subgrouping approach has been used at St. Jude and affiliated centers to identify patients whose cancer is driven by mutations in the sonic hedgehog (SHH) pathway and who may benefit from treatment with new SHH antagonists. St. Jude’s neuropathology group also performs this subgrouping assay for multiple other centers across North America, Australia, and Europe that are treating medulloblastoma patients. Dr. Ellison has also helped to establish the assay in several American centers, such as the Mayo Clinic and UCSF.
The patent for this assay, “Medulloblastoma Subtyping Assay (SJ-10-0020),” was issued on April 14, 2015. It describes methods for determining the immunophenotype of a medulloblastoma by detecting expression of GAB1, filamin A, or at least two biomarker proteins selected from the group consisting of .beta.-catenin, YAP1, GAB1, and filamin A, and typing the medulloblastoma as a WNT pathway tumor, a SHH pathway tumor, or a non-WNT/non-SHH tumor based on this immunophenotype. The assay would type the tumor and also contain instructions for use, reagents for detecting antibody binding to the biomarker proteins, and control samples.
Medulloblastoma, subtype, assay, screening, drug, neuropathology
Granted patents or published applications
U.S. Patent No. 9,005,907 granted April 14, 2015.
Related scientific references
Results of two clinical studies which utilized this assay were recently reported in Robinson, G. et al., “Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032”, Journal of Clinical Oncology 33(24): 2646-2654 (August 10, 2015);
Ellison, D., Acta Neuropathology 121(3): 381-396 (Jan. 26, 2011);
Ellison, D., Acta Neuropathology 120:305-316 (July 23, 2010).
We are currently seeking a committed partner to help us further develop this technology into a companion diagnostic for medulloblastoma treatments that are subgroup-specific. The use of this assay to identify patients eligible to be treated with a SHH antagonist in clinical trials should be of specific interest to improve treatment or develop therapeutic interventions for medulloblastoma. This would also apply equally to WNT pathway antagonists, some of which are currently being developed. Contact: firstname.lastname@example.org
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