Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses.

Fiche publication

Date publication

septembre 2026

Journal

Molecular therapy. Oncology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LAVERNY Gilles

Tous les auteurs :
Fauveau C, Lawendy E, Deforges J, Cochin S, Moreau B, Balloul JM, Erbs P, Jain S, Laverny G,

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42438683

Résumé

Drug resistance remains a major burden in clinical care, often emerging from a subpopulation of cells in a drug-tolerant state. In this study, we aimed to characterize the transcriptional features of persistent non-small cell lung cancer (NSCLC) cells following cisplatin-pemetrexed chemotherapy and explore the therapeutic potency of oncolytic viruses to eliminate these cells. We established a 3D spheroid model of NSCLC and applied long-term chemotherapy to induce a reversible, non-proliferative persistent state associated with lower sensitivity to treatment. Single-cell RNA sequencing coupled with comparative analysis of multiple human datasets sheds light on a core transcriptional signature of persistence. This signature was enriched in patient-derived minimal residual disease (MRD) datasets, highlighting the clinical relevance of persistent preclinical models. Furthermore, transcriptomic analyses suggested a vulnerability of persister cells to oncolytic viruses, a finding validated in spheroid and patient-derived organoids. Altogether, these results define a conserved persistence signature and support the use of virotherapy as a promising option to target MRD.