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      Clinical Research for Pediatric Patients Suffering from a Diffuse Midline Glioma: Limits, Challenges and Perspectives

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      conference-abstract
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      REPO4EU
      RExPO23
      25-26 October 2023
      Clinical trials, pediatric, midline glioma
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            Abstract

            Diffuse midline glioma (DMG) remain lethal tumors with virtually no long-term survivors and a reported median survival of 11 months. The majority of patients are less than 10 years of age at time of diagnosis. Due to their delicate location and diffuse appearance, resection is not feasible. Standard treatment includes biopsy followed by focal radiation therapy and clinical trial enrollment given the lack of standard of care options.

            Unfortunately, translation of promising preclinical results into the clinic has been not successful. Although some genetic markers have been identified that correlate with prognosis, only few approaches make use of precision medicine tools to consult individual, targeted therapies. Key challenges to improve outcome for these hard-to-treat tumors are (1) need for international collaborations given disease rarity, (2) lack of industry interest, (3) access to agents that cross the blood brain barrier, and (4) limitations to conduct trials that allow interrogation of on treatment tumor tissue to better understand impact of new therapies.

            In 2019 the DMG/DIPG center Zurich at the University Children’s Hospital Zurich was established with the goal to change the therapeutic approach to DMGs through close collaboration between the clinic and laboratory. Since then, we have established a large international DMG focused network aimed at developing new therapies. One outcome of this network is the implementation of a first DMG platform trial that enrolls patients internationally. The trial treatment is based on combination therapy options offered at different disease stages that have been validated across multiple laboratories. To address key limitations of prior trials we built in a myriad of correlative studies to develop potential biomarkers of response as well as resistance.

            Given the dismal prognosis, physician and scientists are caught between the expectations of families, the interests of researchers, and regulatory requirements. This results in a variety of challenges on the ethical, scientific and legal side. It is undeniable that for this constellation of a rare disease in a pediatric population, we need to rethink previous approaches and adopt new strategies to make a difference.

            Content

            Author and article information

            Conference
            REPO4EU
            26 September 2023
            Affiliations
            [1 ] University Children’s Hospital Zurich, Oncology, Zurich (Switzerland) ( https://ror.org/035vb3h42)
            [2 ] University of California, San Francisco, Neurology, Neurosurgery and Pediatric (USA) ( https://ror.org/043mz5j54)
            Author information
            https://orcid.org/0009-0001-0105-7127
            https://orcid.org/0000-0002-1783-631X
            https://orcid.org/0000-0002-1154-2732
            https://orcid.org/0000-0003-3136-9241
            https://orcid.org/0000-0002-1951-9828
            https://orcid.org/0000-0002-3452-5150
            Article
            10.58647/REXPO.23012
            f43209a7-bdf8-4b31-b6c9-815f5efe2100
            Authors

            Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.

            RExPO23
            2
            Stockholm, Sweden
            25-26 October 2023
            History
            Product

            REPO4EU

            Categories

            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Pharmacology & Pharmaceutical medicine
            Clinical trials,pediatric,midline glioma

            References

            1. Mueller Timothy, Laternser Sandra, Guerreiro Stücklin Ana S., Gerber Nicolas U., Mourabit Sulayman, Rizo Marion, Rushing Elisabeth J., Kottke Raimund, Grotzer Michael, Krayenbühl Niklaus, Nazarian Javad, Mueller Sabine. Real-time drug testing of paediatric diffuse midline glioma to support clinical decision making: The Zurich DIPG/DMG centre experience. European Journal of Cancer. Vol. 178:171–179. 2023. Elsevier BV. [Cross Ref]

            2. Di Ruscio Valentina, Del Baldo Giada, Fabozzi Francesco, Vinci Maria, Cacchione Antonella, de Billy Emmanuel, Megaro Giacomina, Carai Andrea, Mastronuzzi Angela. Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle. Diagnostics. Vol. 12(9)2022. MDPI AG. [Cross Ref]

            3. Miguel Llordes Gloria, Medina Pérez Víctor Manuel, Curto Simón Beatriz, Castells-Yus Irene, Vázquez Sufuentes Silvia, Schuhmacher Alberto J.. Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma. Journal of Clinical Medicine. Vol. 12(16)2023. MDPI AG. [Cross Ref]

            4. Power Erica A., Rechberger Julian S., Gupta Sumit, Schwartz Jonathan D., Daniels David J., Khatua Soumen. Drug delivery across the blood-brain barrier for the treatment of pediatric brain tumors – An update. Advanced Drug Delivery Reviews. Vol. 185:2022. Elsevier BV. [Cross Ref]

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