Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses
Year: 2026
Type: article
Abstract: 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.
Source: Molecular Therapy Oncology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Funders: European Bioinformatics Institute, European Federation of Pharmaceutical Industries and Associations, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche, Centre National de la Recherche Scientifique, Institut National Du Cancer
Awards: G1109023570, G1443766078, G164444715, G1691837502, G1800105685, G1923432458, G1949054838, Par-delà les frontières, l'Université de Strasbourg, G2255650664, G2449524460, G2659019386, G2694206344, Façonner les talents en formation et en recherche à l'Université de Strasbourg, G2980570810, G3000920764, G3310169441, G3357951378, G3674634315, G3730343, G399734812, Building a reproducible single-cell experimental workflow to capture tumour cell persistence, G4381811279, Integrative Molecular and Cellular Biology, G471331628, G4779185514, G4798114250, G4899307531, G4941046983, Integrative Biology : Nuclear dynamics- Regenerative medicine - Translational medicine, G6136357505, G6276897512, G6364173891, G6803667113, G7002111755, G7092843883, G7240651115, G7304210533, G7373458342, G7376787254, G7804020939, G8031520463, G8709294526
OpenAlex ID: W7165393507