Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma
Diffuse midline glioma (DMG) is a pediatric brain cancer that has a dismal prognosis with limited treatment options. We present the treatment course and outcome of an adolescent male diagnosed with a thalamic DMG carrying a histone H3.3 K27M (H3K27M) alteration. Tumor biopsies were taken at diagnosi...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1606575/full |
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| author | Philip K. Tan Philip K. Tan Timothy J. Martins Pamela S. Becker Pamela S. Becker Pamela S. Becker Robert J. Wechsler-Reya Robert J. Wechsler-Reya John Ross Crawford John Ross Crawford John Ross Crawford |
| author_facet | Philip K. Tan Philip K. Tan Timothy J. Martins Pamela S. Becker Pamela S. Becker Pamela S. Becker Robert J. Wechsler-Reya Robert J. Wechsler-Reya John Ross Crawford John Ross Crawford John Ross Crawford |
| author_sort | Philip K. Tan |
| collection | DOAJ |
| description | Diffuse midline glioma (DMG) is a pediatric brain cancer that has a dismal prognosis with limited treatment options. We present the treatment course and outcome of an adolescent male diagnosed with a thalamic DMG carrying a histone H3.3 K27M (H3K27M) alteration. Tumor biopsies were taken at diagnosis for histological analysis, molecular profiling, and ex vivo drug sensitivity testing (DST). Seven months after diagnosis, the patient had recurrent/progressive disease after radiotherapy and an ineffective molecular-guided therapy based on tumor molecular profiling. The patient then started a novel functional precision medicine (FPM)-guided two-drug combination of disulfiram, based on the DST results of this drug on the patient’s tumor cells obtained at diagnosis, and ONC 201, the only drug that has advanced to a phase III clinical trial for H3K27M-DMG. Neuroimaging demonstrated a treatment response, and the patient lived for fifteen months after starting this personalized therapy. Disulfiram was discontinued after three months due to significant peripheral neuropathy. Our case describes the feasibility and limitations of using DST of patient-derived tumor cells to identify potentially effective personalized and novel therapies for DMG, which should be evaluated for efficacy and safety in formal N-of-1 clinical trials settings. We discuss the benefits and risks of this approach, particularly considering its use in children, adolescents, and young adults with pediatric brain cancers. |
| format | Article |
| id | doaj-art-e81e42c04b6345f68b4e8095760c32a5 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e81e42c04b6345f68b4e8095760c32a52025-08-20T03:59:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16065751606575Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline gliomaPhilip K. Tan0Philip K. Tan1Timothy J. Martins2Pamela S. Becker3Pamela S. Becker4Pamela S. Becker5Robert J. Wechsler-Reya6Robert J. Wechsler-Reya7John Ross Crawford8John Ross Crawford9John Ross Crawford10The Cure Starts Now Foundation, Cincinnati, OH, United StatesYuvaan Tiwari Foundation, Atlanta, GA, United StatesInstitute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, United StatesDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, United StatesDepartment of Hematologic Malignancies Translational Science, City of Hope National Medical Center, Duarte, WA, United StatesDepartment of Medicine, University of Washington, Seattle, WA, United StatesCancer Genome and Epigenetics Program, National Cancer Institute (NCI)-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesDepartment of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, United StatesRady Children’s Hospital, San Diego, CA, United States0Children’s Hospital of Orange County, Orange, CA, United States1Department of Pediatrics and Neurology, University of California Irvine, Irvine, CA, United StatesDiffuse midline glioma (DMG) is a pediatric brain cancer that has a dismal prognosis with limited treatment options. We present the treatment course and outcome of an adolescent male diagnosed with a thalamic DMG carrying a histone H3.3 K27M (H3K27M) alteration. Tumor biopsies were taken at diagnosis for histological analysis, molecular profiling, and ex vivo drug sensitivity testing (DST). Seven months after diagnosis, the patient had recurrent/progressive disease after radiotherapy and an ineffective molecular-guided therapy based on tumor molecular profiling. The patient then started a novel functional precision medicine (FPM)-guided two-drug combination of disulfiram, based on the DST results of this drug on the patient’s tumor cells obtained at diagnosis, and ONC 201, the only drug that has advanced to a phase III clinical trial for H3K27M-DMG. Neuroimaging demonstrated a treatment response, and the patient lived for fifteen months after starting this personalized therapy. Disulfiram was discontinued after three months due to significant peripheral neuropathy. Our case describes the feasibility and limitations of using DST of patient-derived tumor cells to identify potentially effective personalized and novel therapies for DMG, which should be evaluated for efficacy and safety in formal N-of-1 clinical trials settings. We discuss the benefits and risks of this approach, particularly considering its use in children, adolescents, and young adults with pediatric brain cancers.https://www.frontiersin.org/articles/10.3389/fonc.2025.1606575/fulldiffuse midline gliomafunctional precision medicinedrug sensitivity testingmolecular guided therapypediatric brain cancer |
| spellingShingle | Philip K. Tan Philip K. Tan Timothy J. Martins Pamela S. Becker Pamela S. Becker Pamela S. Becker Robert J. Wechsler-Reya Robert J. Wechsler-Reya John Ross Crawford John Ross Crawford John Ross Crawford Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma Frontiers in Oncology diffuse midline glioma functional precision medicine drug sensitivity testing molecular guided therapy pediatric brain cancer |
| title | Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma |
| title_full | Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma |
| title_fullStr | Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma |
| title_full_unstemmed | Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma |
| title_short | Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma |
| title_sort | case report application of ex vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma |
| topic | diffuse midline glioma functional precision medicine drug sensitivity testing molecular guided therapy pediatric brain cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1606575/full |
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