| Title: |
Molecularly guided therapies for advanced primary liver cancers refractory to systemic treatment: Results from the 2025 French Genomic Medicine Initiative |
| Authors: |
Campani, Claudia; Puig, P. Laurent; Villeret, F.; Benmerabet, Y.; Netter, J.; Chouik, Y.; Spitzer, E.; Merle, P.; Bousquet, G.; Ziol, M.; Asif-Laidin, A.; Seror, O.; Ganne-Carrie, N.; Nahon, P.; Omar, A. Ait; Marisa, L.; Lequoy, M.; Bouattour, M.; Tlemsani, C.; Ningarhari, M.; Allaire, M.; Zucman-Rossi, J.; Nault, J.C. |
| Contributors: |
Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité); Università degli Studi di Firenze = University of Florence = Université de Florence (UniFI); Laboratoire de Biologie Médicale SeqOIA Paris (seqOIA); Cancer Research and Personalized Medicine - CARPEM Paris (SIRIC CARPEM); Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer (INCa)-Université Paris Cité (UPCité); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO); Hôpital de la Croix-Rousse CHU - HCL; Hospices Civils de Lyon (HCL); Hôpital Beaujon AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Sorbonne Université (SU); Hôpital Avicenne AP-HP; Centre de Recherche Saint-Antoine (CRSA); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition CHU Pitié Salpêtrière (IHU ICAN); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Hôpital Cochin AP-HP; Hôpital Claude Huriez Lille; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); ANR-21-RHUS-0001,DELIVER,Deliver therapeuthic innovation for advanced hepatic diseases(2021); ANR-23-RHUS-0014,Livertrack,exTRACellular vesicles as biomarKers(2023); ANR-22-CE17-0021,SYSTHEC,Prédiction de la réponse aux traitements systémiques du carcinome hépatocellulaire(2022); European Project: 101096312,HORIZON-MISS-2021-CANCER-02,HORIZON-MISS-2021-CANCER-02,GENIAL(2023) |
| Source: |
ISSN: 0168-8278. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2026 |
| Subject Terms: |
Biomarkers; Primary Liver Tumors; Precision Medicine; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology |
| Description: |
International audience ; Background & Aims: Advanced primary liver cancers (hepatocellular carcinoma (HCC), combined hepatocellular-cholangiocarcinoma (cHCC-CCA), cholangiocarcinoma (CCA), fibrolamellar carcinoma (FLC), hepatic sarcoma (HS), and epithelioid haemangioendothelioma (HEHE) remain difficult to treat after failure of first-line therapy. The 2025 French Genomic Medicine Initiative aimed to identify actionable targets for personalized treatment. Methods: Patients with PLC progressing on systemic therapy were enrolled across eight centers. Tumor and blood samples were analyzed using whole-genome, whole-exome, and RNA sequencing to identify targetable alterations classified using ESCAT scale. Genomic results and potential therapies were reviewed by a molecular tumor board. Results: A total of 120 patients were enrolled: 80 HCC, 25 CCA, 9 cHCC-CCA, 4 FLC, 1 HS, and 1 HEHE. Genomic alterations included TP53 (46%), TERT (44%), and CTNNB1 (20%) in HCC; TP53 (55%), ARID1A (20%), and BAP1 in CCA; TP53 (67%), PIK3CA (22%), and ARID2 (11%) in cHCC-CCA.Among 103 interpretable genomes, 67 patients harbored at least one actionable alteration (HCC: 59%, CCA: 80%, cHCC-CCA: 78%). Thirty-one patients (22 HCC, 5 CCA, 3 cHCC-CCA, 1 HEHE, 1 HS) received matched therapies: 1 ESCAT I, 2 ESCAT II, 21 ESCAT III, and 7 ESCAT IV. These patients had received prior systemic therapy including two lines or more in 69% of the cases. Disease control (DC; radiological response/stable disease) was achieved in 10 of 31 patients (32.3%), including 23% of HCC, 75% of CCA, and 67% of cHCC-CCA cases. DC was observed exclusively in patients treated for ESCAT I-III alterations (41.7%), with no clinical benefit in those treated for ESCAT IV alterations. Median progression-free survival was significantly longer in patients achieving DC compared with those with progressive disease (11.8 vs. 2.4 months; p=0.009) Conclusions: Comprehensive genomic profiling in advanced PLC refractory to systemic treatments is feasible and associated with ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41865801; info:eu-repo/grantAgreement//101096312/EU/Understanding Gene ENvironment Interaction in ALcohol-related hepatocellular carcinoma/GENIAL; PUBMED: 41865801 |
| DOI: |
10.1016/j.jhep.2026.03.019 |
| Availability: |
https://hal.sorbonne-universite.fr/hal-05577789; https://hal.sorbonne-universite.fr/hal-05577789v1/document; https://hal.sorbonne-universite.fr/hal-05577789v1/file/PIIS0168827826001455.pdf; https://doi.org/10.1016/j.jhep.2026.03.019 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.5ECE2EFE |
| Database: |
BASE |