Journal Article (Review Article)

DKFZ-2026-01709

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Paediatric therapeutic development workshop on medulloblastoma.

Montiel Equihua, C. ; Baxter, J. S. ; Molenaar, J. J. ; Areso, I. ; Abbou, S. ; Anderson, J. ; Andre, N. ; Ayrault, O. ; Blanc, P. ; Carpenter, N. ; Daems, S. ; D'Angiolella, V. ; Danielson, L. ; Donovan, L. ; Durbin, A. D. ; Fouladi, M. ; Gajjar, A. ; Gilbertson, R. ; Giraud, G. ; Gottardo, N. ; Hill, R. ; Kearns, P. ; Kool, M. ; Lass, G. ; Marino, S. ; Mueller, S. ; Newman, S. ; Olson, J. ; Patel, S. ; Pfister, S.DKFZ* ; Rainsbury, J. ; Ramaswamy, V. ; Rutkowski, S. ; Straathof, K. ; Swartling, F. J. ; Wechsler-Reya, R. J. ; Pearson, A. D. J. ; Jenkinson, D. ; Doz, F. ; Clifford, S. C. ; LifeArc (Collaboration Author) ; Cancer, I. T. f. C. w. (Collaboration Author) ; UK, C. R. (Collaboration Author) ; team, C. G. C. P. (Collaboration Author) ; BaxterMolenaarPatelBlanc, J. S. J. (Contributor) ; AresoKearnsDaems, I. (Contributor) ; Lass, G. (Contributor) ; Pearson, A. D. J. (Contributor) ; Jenkinson, D. (Contributor)

2026
Nature Publ. Group Edinburgh

Abstract: 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.

Note: #DKTKZFB26# / #NCTZFB26# / epub

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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