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Publications

Journal Article Review Ahead of print

PubMed: 42288687 DOI: 10.1038/s41416-026-03483-1

Paediatric Therapeutic Development Workshop on rhabdomyosarcoma.

Br J Cancer

Authors: Joseph S Baxter, Claudia Montiel Equihua, Jan J Molenaar, Jamie Aye, Gianni Bisogno, Patricia Blanc, Willemijn Breunis, Julia Chisholm, Jacquelyn Crane, Sam Daems, Laura Danielson, Bram de Wilde, Adam D Durbin, Felipe Galvez-Cancino, Patrizia Gasparini, Birgit Geoerger, Simone Graham, Bass Hassan, Mark E Hatley, Delphine Heenen, Christine M Heske, Simone Hettmer, Elizabeth Hookham, Peter Houghton, Pamela Kearns, Charles Keller, Javed Khan, Fiona Kinnis, David Langenau, Geffen Lass, Corinne Mary Linardic, Leo Mascarenhas, Michael T Meister, Jonathan Metts, Véronique Minard-Colin, Sapna Oberoi, Daniela Palacios, Abbe Pannucci, Seema Patel, Sheena Patel, Silvia Pomella, Terry Rabbitts, Rossella Rota, Erin Rudzinski, Beat Schäfer, John Jack Shern, Karin Straathof, Rajkumar Venkatramani, Marco Wachtel, Sara Wakeling … and 7 other authors

Affiliations

  • LifeArc, London, UK.
  • Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • The University of Alabama at Birmingham, Birmingham, AL, USA.
  • Department of Women's and Children's Health, University of Padova and Pediatric Hematology Oncology Unit, University Hospital of Padova, Padua, Italy.
  • Imagine for Margo, Paris, France.
  • University Children's Hospital Zurich, Zürich, Switzerland.
  • The Royal Marsden Hospital and Institute of Cancer Research, Sutton, UK.
  • Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Waterland Private Equity Investments, Antwerp, Belgium.
  • I3h Institute, Université libre de Bruxelles, Brussels, Belgium.
  • Cancer Research UK, London, UK.
  • Ghent University Hospital, Gent, Belgium.
  • St Jude Children's Research Hospital, Memphis, TN, USA.
  • Laboratory of Immune-Regulation, Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
  • Gustave Roussy, Paris, France.
  • Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • KickCancer Foundation, Brussels, Belgium.
  • Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Pediatrics I, Martin-Luther University Halle-Wittenberg, Halle, Germany.
  • UT Health San Antonio, San Antonio, TX, USA.
  • College of Medicine and Health, University of Birmingham, Birmingham, UK.
  • Innovative Therapies for Children and Adolescents with Cancer (ITCC), Paris, France.
  • Children's Cancer Therapy Development Institute, Hillsboro, OR, USA.
  • Oncogenomics Section, Genetics Branch, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Massachusetts General Hospital - Charlestown Navy Yard (CNY) Campus, Charlestown, MA, USA.
  • Department of Pediatrics, Duke University School of Medicine, LSRC, Durham, NC, USA.
  • Cedars Sinai, Los Angeles, CA, USA.
  • Johns Hopkins All Children's Cancer & Blood Disorders Institute, Saint Petersburg, FL, USA.
  • Max Rady College of Medicine, Pediatrics and Child Health, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
  • Institute for Systems Analysis and Computer Science "Antonio Ruberti" (IASI), National Research Council (CNR), Rome, Italy.
  • Alice's Arc, New York City, NY, USA.
  • Cancer Research Horizons, London, UK.
  • Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy.
  • The Institute of Cancer Research, Brookes Lawley Building, Centre for Cancer Drug Discovery, Sutton, UK.
  • Indiana University School of Medicine, Indianapolis, IN, USA.
  • Universitäts-Kinderspital Zürich, Eleonorenstiftung, Zürich, Switzerland.
  • Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • University College London Cancer Institute, Great Ormond Street Biomedical Research Centre, London, UK.
  • Texas Children's Hospital, Houston, TX, USA.
  • Alice's Ark, Children's Cancer Charity, Sevenoaks, UK.

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.

MeSH

Cells, Rhabdomyosarcoma, Antigens, Surface, Pharmaceutical Preparations, Neoplasms, Sarcoma, Therapeutics, Child