Paediatric Therapeutic Development Workshop on rhabdoid tumours

TY - JOUR

T1 - Paediatric Therapeutic Development Workshop on rhabdoid tumours

AU - Montiel Equihua, Claudia

AU - Molenaar, Jan J.

AU - Areso, Itziar

AU - Biegel, Jaclyn A.

AU - Blanc, Patricia

AU - Chi, Susan N.

AU - Daems, Sam

AU - Danielson, Laura

AU - Drost, Jarno

AU - Franke, Niels E.

AU - Frühwald, Michael C.

AU - Gajjar, Amar

AU - Geller, James I.

AU - Huang, Annie

AU - Johann, Pascal D.

AU - Kearns, Pamela

AU - Nysom, Karsten

AU - O’Connor, Suzanne

AU - Ortiz, Michael V.

AU - Parker, Jenny

AU - Patel, Seema

AU - Patel, Sheena

AU - Roberts, Charles WM

AU - Williamson, Daniel

AU - Yi, Joanna S.

AU - Pearson, Andrew D.J.

AU - Jenkinson, David

AU - Kool, Marcel

AU - Bourdeaut, Franck

N1 - Publisher Copyright: © The Author(s) 2026.

PY - 2026/2/12

Y1 - 2026/2/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105031932246

U2 - 10.1038/s41416-026-03348-7

DO - 10.1038/s41416-026-03348-7

M3 - Review article

C2 - 41680284

AN - SCOPUS:105031932246

SN - 0007-0920

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -