Portal de investigación
Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Henriksen, TV
- Frydendahl, A
- Gotchalck, KA
- Tébar-Martínez, R
- Andersen, CL
Grupos y Plataformas de I+D+i
Abstract
In stage 2-3 colon cancer (CC), postsurgery circulating tumor DNA (ctDNA) assessment is crucial for guiding adjuvant chemotherapy (ACT) decisions. While existing assays detect ctDNA and help identify high-risk persons with CC for recurrence, their limited sensitivity after surgery poses challenges in deciding on ACT. Additionally, a substantial portion of persons with CC fail to clear ctDNA after ACT, leading to recurrence. In this study, we performed whole-exome sequencing (WES) of ctDNA at different time points in participants with relapsed CC in two independent cohorts, alongside transcriptomic and proteomic analyses of metastases, to enhance comprehension of progression mechanisms. A plasma WES-based tumor-agnostic assay demonstrated higher sensitivity in detecting minimal residual disease (MRD) compared to current assays. Immune evasion appears to be the primary driver of progression in the localized CC setting, indicating the potential efficacy of immunotherapy for microsatellite stability in persons with CC. Organoid modeling further supports the promising potential of targeted therapy in eradicating MRD, surpassing conventional treatments.
Datos de la publicación
- ISSN/ISSNe:
- 2662-1347, 2662-1347
- Tipo:
- Article
- Páginas:
- 1000-1016
- PubMed:
- 40301653
Nature Cancer NATURE PORTFOLIO
Citas Recibidas en Web of Science: 3
Documentos
Filiaciones
Filiaciones no disponibles
Financiación
Proyectos y Estudios Clínicos
Unidad de biobancos y biomodelos de INCLIVA.
Investigador Principal: ANTONIO FERRANDEZ IZQUIERDO
PT20/00029 . INSTITUTO SALUD CARLOS III . 2021
Cita
Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer. Martín J, Gimeno F, Henriksen TV, García B, Martínez B, Gambardella V, Martínez C et al. Nature Cancer. 2025 junio 01. 6 (6):1000-1016. DOI:10.1038/s43018-025-00960-z. PMID:40301653.
