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Prior therapy defines mutation profiles in childhood cancer at relapse

Nature Medical/Healthcare AI Mehdi Layeghifard, Marcos Díaz-Gay, Erik N. Bergstrom, Mathepan J. Mahendralingam, Nicholas Light, Sasha Blay, Joshua O. Nash, Nathaniel D. Anderson, Jessica N. Au, Scott Davidson, Pedro L. Ballester, Timmy Wen, Syed Kashif Daud, Lisa-Monique Edward, S. M. Ashiqul Islam, Azhar Khandekar, Burçak Otlu, Ledia Brunga, Rawan Hammad, Shimaa Nassif, Nirav H. Thacker, Tara Feltham, Noemi A. Fuentes-Bolanos, Marie Wong-Erasmus, Max F. Levine, Katherine E. Miller, Neerav N. Shukla, Michael D. Kinnaman, Dominik Glodzik, Carol Portwine, Sabrina Millson, Alexandra P. Zorzi, Mariam Mikhail, Conrad V. Fernandez, Laura Wheaton, Gunes Gundem, Andrew L. Kung, Uri Tabori, Chelsea Mayoh, Elli Papaemmanuil, Mark J. Cowley, David Malkin, Anita Villani, Ludmil B. Alexandrov, Adam Shlien 2026-07-22

TL;DR - A Nature study finds that prior chemotherapy—especially platinum-based treatment—rapidly reshapes mutation profiles in relapsed childhood cancers. The findings support exploring safer, de-escalated therapies to reduce treatment-driven tumour evolution.

Chemotherapy was associated with substantial, rapidly detectable mutagenesis.
Platinum-based drugs tripled private mutational signatures.
Treatment doubled the mutation burden in relapsed tumours.
Therapy-induced evolution may influence relapse biology and future treatment design.

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