Loss‐of‐function genetic screen unveils synergistic efficacy of PARG inhibition with combined 5‐fluorouracil and irinotecan treatment in colorectal cancer
LOF screening identified PARG as a modulator of CRC response to FUIRI treatment. HT29 PARG-KO cells showed increased PAR, DNA damage, apoptosis, and 5FU sensitivity. Pharmacological PARG inhibition synergised with 5FU and SN38 in CRC cell lines. HT29 PARG-KO tumours exhibited increased sensitivity to 5FU treatment in vivo. PARG expression in CRC tumours correlated with poorer responses and patient survival.
Authors
- Ferran Grau‐Leal (ORCID: https://orcid.org/0000-0003-3072-2250)
- E. Musulen
- Jeannine Diesch (ORCID: https://orcid.org/0000-0002-4667-3468)
- Marcus Buschbeck (ORCID: https://orcid.org/0000-0002-3218-4567)
- Sara Cabrero‐de las Heras (ORCID: https://orcid.org/0000-0002-9364-5371)
- Cristina Queralt (ORCID: https://orcid.org/0000-0001-9875-0173)
- Cristina Bugés (ORCID: https://orcid.org/0000-0003-2013-1510)
- Johannes Zuber (ORCID: https://orcid.org/0000-0001-8810-6835)
- Marta Costa (ORCID: https://orcid.org/0000-0001-7718-386X)
- José Luis Manzano
- Cristina Moreta‐Moraleda
- Eva Martínez‐Balibrea
- Roni H G Wright
- Sonia‐V Forcales
- Carla Vendrell‐Ayats
Institutions
- Research Institute of Molecular Pathology (AT)
- Universitat Internacional de Catalunya (ES)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Institut Català d'Oncologia (ES)
- Hospital General de Catalunya (ES)
- Badalona Serveis Assistencials (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Vienna Biocenter (AT)
- Hospital Municipal de Badalona (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Clinical and Translational Medicine
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/ctm2.70543
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundación Olga Torres
- Fundación Científica Asociación Española Contra el Cáncer
- Agencia Estatal de Investigación
- HORIZON EUROPE Marie Sklodowska-Curie Actions