Paediatric Therapeutic Development Workshop on rhabdoid tumours

Rhabdoid tumours (RT) are malignancies of the central nervous system, kidneys, liver and soft tissues that most commonly affect very young children with survival rates below 30% in high-risk cohorts. Treatment entails surgery, intensive chemotherapy and radiotherapy, associated with substantial short- and long-term toxicities. There is an unmet need to develop targeted therapies for RT to improve patient outcomes and mitigate the toxicities of current therapy. Detailed research followed by a workshop had the objective of enabling the development of targeted therapeutics for RT. Given the inherent commonality of their biology (i.e. biallelic inactivation of SMARCB1 or more rarely SMARCA4) the therapeutic approach should be similar for intra-cranial and extra-cranial tumours. DDB1-CUL4-associated factor 5 is a promising target, and the development of small molecule binders/degraders is a priority. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) degraders may have greater therapeutic potential than inhibitors. Fibroblast growth factor receptor and platelet-derived growth factor receptor inhibitors may have value in subgroups. Mouse double minute 2 homologue (MDM2) is a priority target for novel therapeutic development and combination trials. Combinations of EZH2, MDM2 inhibitors and selective inhibitors of nuclear export should be evaluated robustly preclinically and drive early clinical studies.

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Journal
British Journal of Cancer
Published
2026-02-12
DOI
https://doi.org/10.1038/s41416-026-03348-7
Primary Topic
Chromatin Remodeling and Cancer
Type
article
Field-Weighted Citation Impact
0.00

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article

Paediatric Therapeutic Development Workshop on rhabdoid tumours

N. Susan, Amar Gajjar, Suzanne O’Connor, Michael C. Frühwald et al.
British Journal of Cancer
Chromatin Remodeling and Cancer
article

Paediatric Therapeutic Development Workshop on rhabdoid tumours

N. Susan, Amar Gajjar, Suzanne O’Connor, Michael C. Frühwald, Laura S. Danielson, K. Nysom, Annie Huang, Pamela R. Kearns, N. Franke, Charles W.M. Roberts, Shreenal Patel, James I. Geller, Michael Vincent Ortiz, Sam Daems, J Jaap Molenaar, Jaclyn A. Biegel, Claudia Montiel Equihua, Joanna S. Yi, Pascal D. Johann, Patricia Blanc, Marcel Kool, Andrew DJ Pearson, Jenny Parker, Itziar Areso, Daniel Williamson, Jarno Drost, Franck Bourdeaut, David Jenkinson, Innovative Therapies for Children with Cancer (ITCC), On behalf of LifeArc, Cancer Grand Challenge PROTECT team
article en

Abstract

Rhabdoid tumours (RT) are malignancies of the central nervous system, kidneys, liver and soft tissues that most commonly affect very young children with survival rates below 30% in high-risk cohorts. Treatment entails surgery, intensive chemotherapy and radiotherapy, associated with substantial short- and long-term toxicities. There is an unmet need to develop targeted therapies for RT to improve patient outcomes and mitigate the toxicities of current therapy. Detailed research followed by a workshop had the objective of enabling the development of targeted therapeutics for RT. Given the inherent commonality of their biology (i.e. biallelic inactivation of SMARCB1 or more rarely SMARCA4) the therapeutic approach should be similar for intra-cranial and extra-cranial tumours. DDB1-CUL4-associated factor 5 is a promising target, and the development of small molecule binders/degraders is a priority. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) degraders may have greater therapeutic potential than inhibitors. Fibroblast growth factor receptor and platelet-derived growth factor receptor inhibitors may have value in subgroups. Mouse double minute 2 homologue (MDM2) is a priority target for novel therapeutic development and combination trials. Combinations of EZH2, MDM2 inhibitors and selective inhibitors of nuclear export should be evaluated robustly preclinically and drive early clinical studies.

British Journal of Cancer
LifeArc (GB), University of Southern California (US), Cincinnati Children's Hospital Medical Center (US), St. Jude Children's Research Hospital (US), Université Libre de Bruxelles (BE), Memorial Sloan Kettering Cancer Center (US), Children's Hospital of Los Angeles (US), University of Dundee (GB), German Cancer Research Center (DE), Utrecht University (NL), Université Paris Cité (FR), Heidelberg University (DE), Cancer Research UK (GB), Hospital for Sick Children (CA), University Hospital Augsburg (DE), Copenhagen University Hospital (DK), Rigshospitalet (DK), University Medical Center Utrecht (NL), University College Birmingham (GB), Pearson (United Kingdom) (GB), iXBlue (France) (FR), Innovative Clinical Research (US), Oncode Institute (NL), Hopp Children's Cancer Center Heidelberg (DE), Cancer Research Horizons (GB), Princess Máxima Center (NL), SickKids Foundation (CA), Molecular Oncology (United States) (US), Children's Cancer Center (US), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), Deutsches Konsortium für Translationale Krebsforschung (DE), University of Cincinnati (US), University of Birmingham (GB), Institut Curie (FR), Newcastle University (GB)
LifeArc
Openalex Percentile: Top 58%
Chromatin Remodeling and Cancer
DOIOpen Access PDFOpenAlex
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