Paediatric Therapeutic Development Workshop on rhabdomyosarcoma

The third in a series of Paediatric Therapeutic Development Workshops focused on rhabdomyosarcoma. Rhabdomyosarcoma is the most common soft tissue sarcoma in children, with 90% survival for those with the lowest risk disease, but just 20–30% in children with metastatic disease. An urgent unmet need exists to develop targeted therapeutics for high-risk disease and to reduce the toxicity of treatment. The results of trials of CAR T-cells and ADCs against FGFR4 are awaited with great interest, and developing a FGFR4 degrader is a priority. Directly targeting PAX3::FOXO1 and PAX7::FOXO1 fusion proteins is a high priority. An in vivo study of a MYOD1 degrader approach is required prior to clinical development. Degraders of P300/CBP should be evaluated preclinically with a view to clinical investigation. ROR2 is an interesting target for the L122R mutant MYOD1 rhabdomyosarcoma. Development of a TEAD degrader is a high priority, and this should be evaluated in combination with a Notch inhibitor. Considering targets with existing clinical agents, antibody-drug conjugates targeting cell-surface antigen B7-H3/CD276 are showing preclinical promise in other paediatric cancers and are also deemed a high priority for evaluation in rhabdomyosarcoma. Based on currently available evidence, MEK inhibitors should be evaluated, potentially with BRAF or PI3K inhibitors, in combination with chemotherapy in the maintenance setting. Understanding the mechanism of action underpinning drug combinations, gaining access to therapeutics and optimising clinical trial design will be essential to enable combinatorial testing in patients.

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Publication Details

Journal
British Journal of Cancer
Published
2026-06-13
DOI
https://doi.org/10.1038/s41416-026-03483-1
Primary Topic
Sarcoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
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article

Paediatric Therapeutic Development Workshop on rhabdomyosarcoma

Janet Shipley, David M. Langenau, Sapna Oberoi, Michela Casanova et al.
British Journal of Cancer
Sarcoma Diagnosis and Treatment
article

Paediatric Therapeutic Development Workshop on rhabdomyosarcoma

Janet Shipley, David M. Langenau, Sapna Oberoi, Michela Casanova, P. Blanc, Charles Keller, Javed Khan, Christine M. Heske, Delphine Heenen, Geffen Lass, Abbe Pannucci, Silvia Pomella, Julia Chisholm, Felipe Gálvez‐Cancino, Joseph S. Baxter, Terry Rabbitts, Patrizia Gasparini, Simone Hettmer, Rossella Rota, Brenda J. Weigel, Birgit Geoerger, Andrew D.J. Pearson, Corinne M. Linardic, Pamela R. Kearns, Bram De Wilde, Marco Wachtel, Mark E. Hatley, Sam Warburton, Sara Wakeling, Rajkumar Venkatramani, Leo Mascarenhas, Gianni Bisogno, Sam Daems, Véronique Minard-Colin, J Jaap Molenaar, Laura Danielson, Claudia Montiel Equihua, Willemijn Breunis, Andrew DJ Pearson, David Jenkinson, Innovative Therapies for Children with Cancer (ITCC), On behalf of LifeArc, Cancer Grand Challenge PROTECT team, Peter Houghton, Erin Rudzinski, Zoë Walters, Jonathan Metts, Karin Straathof, Jacquelyn Crane, Simone Graham, Adam D. Durbin, Fiona Kinnis, John Jack Shern, Michael T. Meister, Beat Schäfer, Seema Patel, Jamie Aye, Pamela Kearns, Daniela Palacios, Bass Hassan, Sheena Patel, Elizabeth Hookham
article en

Abstract

The third in a series of Paediatric Therapeutic Development Workshops focused on rhabdomyosarcoma. Rhabdomyosarcoma is the most common soft tissue sarcoma in children, with 90% survival for those with the lowest risk disease, but just 20–30% in children with metastatic disease. An urgent unmet need exists to develop targeted therapeutics for high-risk disease and to reduce the toxicity of treatment. The results of trials of CAR T-cells and ADCs against FGFR4 are awaited with great interest, and developing a FGFR4 degrader is a priority. Directly targeting PAX3::FOXO1 and PAX7::FOXO1 fusion proteins is a high priority. An in vivo study of a MYOD1 degrader approach is required prior to clinical development. Degraders of P300/CBP should be evaluated preclinically with a view to clinical investigation. ROR2 is an interesting target for the L122R mutant MYOD1 rhabdomyosarcoma. Development of a TEAD degrader is a high priority, and this should be evaluated in combination with a Notch inhibitor. Considering targets with existing clinical agents, antibody-drug conjugates targeting cell-surface antigen B7-H3/CD276 are showing preclinical promise in other paediatric cancers and are also deemed a high priority for evaluation in rhabdomyosarcoma. Based on currently available evidence, MEK inhibitors should be evaluated, potentially with BRAF or PI3K inhibitors, in combination with chemotherapy in the maintenance setting. Understanding the mechanism of action underpinning drug combinations, gaining access to therapeutics and optimising clinical trial design will be essential to enable combinatorial testing in patients.

British Journal of Cancer
LifeArc (GB), Pace University (US), Cedars-Sinai Medical Center (US), St. Jude Children's Research Hospital (US), Université Libre de Bruxelles (BE), Children's Hospital of Philadelphia (US), University of Padua (IT), Institute of Cancer Research (GB), Johns Hopkins University (US), The University of Texas at San Antonio Health Science Center (US), Duke University (US), University of Zurich (CH), Ghent University Hospital (BE), Southampton General Hospital (GB), Institut Gustave Roussy (FR), University College Birmingham (GB), University of Alabama at Birmingham (US), University of Oxford (GB), CancerCare Manitoba (CA), Johns Hopkins All Children's Hospital (US), Innovative Clinical Research (US), Institute for Systems Analysis (RU), Royal Marsden Hospital (GB), Bambino Gesù Children's Hospital (IT), Cancer Research Horizons (GB), Princess Máxima Center (NL), St. Charles Hospital (US), University Children's Hospital Zurich (CH), Children's Cancer Therapy Development Institute (US), National Cancer Institute (US), Prostate Cancer UK (GB), Immune Regulation (United Kingdom) (GB), Texas Children's Hospital (US), CRUK Lung Cancer Centre of Excellence (GB), Center for Cancer Research (US), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Institut des Maladies Génétiques Imagine (FR), Anticancer Fund (BE), University of Southampton (GB), Indiana University School of Medicine, University College London (GB), Indiana University – Purdue University Indianapolis (US), Martin Luther University Halle-Wittenberg (DE), University of Birmingham (GB), The University of Texas Health Science Center at Houston (US)
Openalex Percentile: Top 6%
Sarcoma Diagnosis and Treatment
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