This Special Issue will focus on adult hepatopancreatobiliary malignancies and liver metastases, with emphasis on targeted, biomarker-driven, and precision anti-tumor therapy. The intended disease scope includes primary liver cancers, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma; colorectal and non-colorectal liver metastases; gallbladder cancer; extrahepatic bile duct cancers; ampullary and periampullary cancers, where clinically relevant; and pancreatic cancer.

The field is moving from organ-based treatment algorithms toward molecular classification, actionable genomic alterations, immune-tumor interactions, multidisciplinary sequencing, and real-world assessment of treatment value. This issue aims to bring together rigorous clinical, translational, and evidence synthesis work that clarifies how targeted therapy, immunotherapy, locoregional-systemic combinations, and biomarker-informed decision-making can improve selection, timing, sequencing, response assessment, toxicity management, and outcomes in adult liver, biliary tract, and pancreatic cancers.

Suitable submissions include original clinical studies, translational studies using human tissue or clinical datasets, clinical trials, registry and real-world evidence studies, biomarker studies, comparative effectiveness analyses, and systematic reviews, scoping reviews, or meta-analyses. Review papers should be PRISMA-compliant, using PRISMA 2020 or the appropriate PRISMA extension, with transparent search strategy, eligibility criteria, study selection, synthesis methods, and quality or risk-of-bias assessment where applicable.

To preserve the scientific focus of the issue, the following submissions will be outside scope: paediatric studies, animal studies, case reports, commentaries, perspectives, editorials, and non-systematic opinion-based reviews. Purely descriptive reports without a clear adult hepatopancreatobiliary oncology focus will not be prioritized. Cross-cancer or pan-cancer submissions are welcome only when they include a substantial and clearly analyzed component relevant to adult liver, gallbladder, bile duct, pancreatic cancer, or liver metastases.

The issue is intended for medical, surgical, and radiation oncologists, hepatopancreatobiliary surgeons, gastroenterologists, interventional radiologists, pathologists, molecular scientists, clinical trialists, and researchers working at the interface of cancer biology, targeted therapy, and multidisciplinary adult hepatopancreatobiliary oncology.

Indicative themes include:

• Molecular classification and actionable targets in liver, biliary tract, and pancreatic cancers.

• Targeted therapy, immunotherapy, and rational combination strategies.

• Neoadjuvant, adjuvant, perioperative, and conversion treatment approaches.

• Therapy sequencing, resistance mechanisms, and treatment beyond progression.

• Liquid biopsy, radiogenomics, biomarkers of response, toxicity, and recurrence.

• Liver-directed and multidisciplinary strategies for primary and metastatic liver tumors.

• Real-world evidence, clinical trial design, access, value, and implementation challenges in adult hepatopancreatobiliary oncology.

Keywords: Hepatopancreatobiliary cancers, hepatocellular carcinoma, cholangiocarcinoma, gallbladder cancer, pancreatic cancer, liver metastases, targeted therapy, precision oncology