Paediatric therapeutic development workshop on osteosarcoma

The fourth Paediatric Therapeutic Development Workshop focused on osteosarcoma, the most common primary bone cancer in children and young adults. Current treatment of osteosarcoma comprises surgery and chemotherapy. Outcome has shown very little improvement over the last four decades and there are substantial unmet needs including improving survival, especially in metastatic or relapsed disease, and reducing treatment toxicity. There is a lack of new therapeutics in osteosarcoma, with the evaluation of new treatments challenged by complex biology and variation in chemotherapy standard of care regimens. An antibody-drug conjugate (ADC) targeting LRRC15 with an osteosarcoma-relevant payload is a promising therapeutic approach. Small molecule inhibitors and degraders targeting SMARCAL1 should be considered as a very high priority, as it is a target applicable to several high unmet need malignancies. Preclinical evaluation of KIF18A in osteosarcoma models is required. An early phase study of an eIF4A1 inhibitor is warranted. Further preclinical validation of RUNX2 using PROTACs or ADCs is required. Targeting MYC, either indirectly or directly is a high priority. Osteosarcomas have significant genomic instability and impaired DNA repair mechanisms and efforts are ongoing to exploit this vulnerability therapeutically. The goal is that these therapeutic developments will improve survival for patients with osteosarcoma.

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Publication Details

Journal
British Journal of Cancer
Published
2026-08-18
DOI
https://doi.org/10.1038/s41416-026-03572-1
Primary Topic
Protein Degradation and Inhibitors
Type
article
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article

Paediatric therapeutic development workshop on osteosarcoma

Emily K. Slotkin, Martin G. McCabe, Michela Casanova, P. Blanc et al.
British Journal of Cancer
Protein Degradation and Inhibitors
article

Paediatric therapeutic development workshop on osteosarcoma

Emily K. Slotkin, Martin G. McCabe, Michela Casanova, P. Blanc, Brian D. Crompton, Pan Pantziarka, Katia Scotlandi, Geffen Lass, Maia Kavanagh-Williamson, Gemma A. Wilson, Joseph S. Baxter, Damon R. Reed, Richard Görlick, Antonin Marchais, Adrienne M. Flanagan, Andrew D.J. Pearson, Pamela R. Kearns, Sandra J. Strauss, Filemon S. Dela Cruz, Nathalie Gaspar, Stefanie Hecker‐Nolting, Mandy Tseng, Emanuela Palmerini, Lillian M. Guenther, Sybille Mittnacht, J. Andrew Livingston, Sam Daems, Pablo Berlanga, J Jaap Molenaar, Laura Danielson, Ann Graham, John Ligon, Christina Ip-Toma, Claudia Montiel Equihua, Poul H. Sorensen, David Jenkinson, On behalf of LifeArc, Michaela Nathrath, Claudia Valverde, Seema Patel, Sheena Patel, Ryan Roberts, Madina Wane, Quentin Campbell-Hewson, Jeremy Lewin, Walker Smallwood, the Cancer Grand Challenge Protect team, Michael W. Bishop, Isidro Cortes-Ciriano, Lee Helman, Innovative Therapies for Children and Adolescents with Cancer (ITCC)
article en

Abstract

The fourth Paediatric Therapeutic Development Workshop focused on osteosarcoma, the most common primary bone cancer in children and young adults. Current treatment of osteosarcoma comprises surgery and chemotherapy. Outcome has shown very little improvement over the last four decades and there are substantial unmet needs including improving survival, especially in metastatic or relapsed disease, and reducing treatment toxicity. There is a lack of new therapeutics in osteosarcoma, with the evaluation of new treatments challenged by complex biology and variation in chemotherapy standard of care regimens. An antibody-drug conjugate (ADC) targeting LRRC15 with an osteosarcoma-relevant payload is a promising therapeutic approach. Small molecule inhibitors and degraders targeting SMARCAL1 should be considered as a very high priority, as it is a target applicable to several high unmet need malignancies. Preclinical evaluation of KIF18A in osteosarcoma models is required. An early phase study of an eIF4A1 inhibitor is warranted. Further preclinical validation of RUNX2 using PROTACs or ADCs is required. Targeting MYC, either indirectly or directly is a high priority. Osteosarcomas have significant genomic instability and impaired DNA repair mechanisms and efforts are ongoing to exploit this vulnerability therapeutically. The goal is that these therapeutic developments will improve survival for patients with osteosarcoma.

British Journal of Cancer
LifeArc (GB), Arkansas Children's Hospital (US), European Bioinformatics Institute (GB), St. Jude Children's Research Hospital (US), Nationwide Children's Hospital (US), Université Libre de Bruxelles (BE), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), University of British Columbia (CA), University of Miami (US), Utrecht University (NL), Université Paris-Saclay (FR), Peter MacCallum Cancer Centre (AU), Kingston Hospital NHS Trust (GB), Institut Gustave Roussy (FR), TUM Klinikum (DE), University of Manchester (GB), University College Birmingham (GB), University of Florida (US), London Cancer (GB), Innovative Clinical Research (US), Olgahospital (DE), Dana-Farber Cancer Institute (US), Royal National Orthopaedic Hospital NHS Trust (GB), Istituto Ortopedico Rizzoli (IT), Cancer Research Horizons (GB), Princess Máxima Center (NL), Vall d'Hebron Hospital Universitari (ES), Cancer Research UK Manchester Institute (GB), The Christie NHS Foundation Trust (GB), Great North Children's Hospital (GB), CRUK Lung Cancer Centre of Excellence (GB), Klinikum Kassel (DE), The Geneva Foundation (US), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Sylvester Comprehensive Cancer Center (US), Research Institute of Dallas (US), Klinikum Stuttgart (DE), Institut des Maladies Génétiques Imagine (FR), University College London (GB), University of Birmingham (GB), Barnard College (US)
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Protein Degradation and Inhibitors
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