Browse by author
Lookup NU author(s): Dr Rebecca HillORCiD, Professor Steven CliffordORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© The Author(s) 2026. The second Paediatric Therapeutic Development Workshop focused on medulloblastoma. Between 60–70% of patients with medulloblastoma survive, but survivors have significant long-term side effects, and the highest-risk groups have a probability of survival <10%. Thus, the unmet need is to develop therapeutics targeting specific vulnerabilities in medulloblastoma including poor prognosis disease groups (SHH-medulloblastoma, MYCN amplified or TP53 mutated; and Group 3 medulloblastoma, c-MYC amplified) and developing less-toxic therapies for good prognosis disease (WNT-medulloblastoma). The Workshop concluded that (i) targeting SRC by a degrader is a high priority, (ii) inhibition of c-MYC and MYCN tumour-relevant functions for poor prognosis groups is a priority, (iii) targeting WNT-medulloblastoma via a radiolabelled theranostic antibody is an innovative approach for good prognosis tumours to further reduce toxicity, and (iv) B7-H3 has many advantages for CAR T-cell and ADC-based approaches. Based on currently available evidence, combinations of central nervous system penetrant selective PARP-1, CHK1/2 or CDK9 inhibitors with an ATR inhibitor could potentially be evaluated in early-phase trials for high-risk patients; however, these combinations require robust evaluation in pre-clinical models first. Early-phase clinical studies should be international, have novel designs to address small patient numbers and based on an understanding of biology with correlative biological studies. Both developing therapeutics targeting specific vulnerabilities in medulloblastoma and evaluating combinations of existing medicinal products are required to improve outcome and reduce long term sequalae.
Author(s): Montiel Equihua C, Baxter JS, Molenaar JJ, Abbou S, Anderson J, Andre N, Ayrault O, Blanc P, Carpenter N, Daems S, D'Angiolella V, Danielson L, Donovan L, Durbin AD, Fouladi M, Gajjar A, Gilbertson R, Giraud G, Gottardo N, Hill R, Kearns P, Kool M, Marino S, Mueller S, Newman S, Olson J, Patel S, Pfister SM, Rainsbury J, Ramaswamy V, Rutkowski S, Straathof K, Swartling FJ, Wechsler-Reya RJ, Jenkinson D, Doz F, Clifford SC, Jenkinson D, Pearson ADJ, Lass G, Areso I, Baxter JS, Kearns P
Publication type: Review
Publication status: Published
Journal: British Journal of Cancer
Year: 2026
Pages: Epub ahead of print
Online publication date: 09/07/2026
Acceptance date: 17/06/2026
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41416-026-03533-8
DOI: 10.1038/s41416-026-03533-8
Data Access Statement: No new scientific data were generated or analysed for this commentary and all data are within the paper.
