Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses
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.
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BibTeX
@article{fauveau2026dissecting,
title = {{Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses}},
author = {Clara Fauveau and Emily Lawendy and Jules Deforges and Sandrine Cochin and Baptiste Moreau and Jean-Marc Balloul and Philippe Erbs and Shreyansh Jain and Gilles Laverny},
journal = {Molecular Therapy: Oncology},
year = {2026},
month = jul,
doi = {10.1016/j.omton.2026.201279},
url = {https://univoak.hal.science/hal-05758136v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses
AU - Clara Fauveau
AU - Emily Lawendy
AU - Jules Deforges
AU - Sandrine Cochin
AU - Baptiste Moreau
AU - Jean-Marc Balloul
AU - Philippe Erbs
AU - Shreyansh Jain
AU - Gilles Laverny
PY - 2026
DA - 2026/07/07
JO - Molecular Therapy: Oncology
DO - 10.1016/j.omton.2026.201279
UR - https://univoak.hal.science/hal-05758136v1
AB - 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.
SN - 2950-3299
ER -