Publication Name	World Journal of Gastroenterology
Manuscript ID	111528
Country	Italy

Category	Gastroenterology & Hepatology
Manuscript Type	Minireviews
Article Title	Post-immunotherapy second-line strategies for hepatocellular carcinoma: State of the art and ongoing trials
Manuscript Source	Invited Manuscript
All Author List	Sara Ascari, Rusi Chen, Andrea De Sinno, Bernardo Stefanini, Matteo Cescon, Matteo Serenari, Cristina Mosconi and Francesco Tovoli
Funding Agency and Grant Number
Corresponding Author	Francesco Tovoli, Associate Professor, MD, Division of Internal Medicine, Hepatobiliary and Immunoallergic Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna 40138, Emilia-Romagna, Italy. francesco.tovoli2@unibo.it
Key Words	Hepatocellular carcinoma; Immune checkpoint inhibitors; Second-line therapy; Post-immunotherapy progression; Tyrosine kinase inhibitors; Bispecific antibodies; Adoptive T-cell therapy; Chimeric antigen receptor-T cells; Treatment sequencing; Clinical trials
Core Tip	Patients with hepatocellular carcinoma progressing after frontline immunotherapy represent an emerging clinical challenge. This review critically explores the current second-line strategies under investigation, including tyrosine kinase inhibitors, novel immune checkpoint inhibitor-based regimens, bispecific antibodies, and adoptive T-cell therapies. Most approaches are supported by strong biological rationale, although high-quality comparative data are still lacking. The multiplicity of ongoing trials underscores the need for a better understanding of resistance mechanisms and therapeutic sequencing. This review may assist clinicians and researchers in interpreting the evolving landscape and in identifying future directions for personalized, effective post-immunotherapy management.
Citation	Ascari S, Chen R, De Sinno A, Stefanini B, Cescon M, Serenari M, Mosconi C, Tovoli F. Post-immunotherapy second-line strategies for hepatocellular carcinoma: State of the art and ongoing trials. World J Gastroenterol 2025; In press

Received	2025-07-02 02:00
Peer-Review Started	2025-07-02 02:00
First Decision by Editorial Office Director	2025-09-12 07:01
Return for Revision	2025-09-12 07:01
Revised	2025-09-25 22:40
Publication Fee Transferred
Second Decision by Editor	2025-12-08 02:36
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2025-12-08 07:37
Articles in Press	2025-12-08 07:37
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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