Innovative Therapeutic Strategies, Biomarkers, and Molecular Pathways in Gastrointestinal and Hepatobiliary Cancers

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Gastrointestinal Oncology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 2825

Special Issue Editors


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Guest Editor
Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA
Interests: gastric cancer; esophageal cancer; colon cancer; hepatocellular carcinoma; bile duct cancer
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA
Interests: gastrointestinal pathology; anatomic and clinical pathology; molecular genetic pathology

Special Issue Information

Dear Colleagues,

Gastrointestinal and hepatobiliary cancers represent a significant global health challenge due to their high morbidity and mortality rates. This Special Issue explores the latest advancements in therapeutic strategies, emphasizing innovative approaches such as immunotherapy, targeted therapies, and combination treatments. Additionally, it highlights emerging biomarkers that facilitate early diagnosis, prognosis, and personalized medicine. The Special Issue also delves into the molecular pathways driving tumorigenesis, uncovering potential targets for drug development. By bringing together cutting-edge research and clinical insights, this collection aims to inspire breakthroughs in managing and treating these complex malignancies, fostering a deeper understanding of their underlying mechanisms and therapeutic potential.

Dr. Anwaar Saeed
Dr. Azhar Saeed
Guest Editors

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Keywords

  • gastrointestinal cancers
  • hepatobiliary cancers
  • immunotherapy
  • targeted therapies
  • combination treatments
  • biomarkers
  • early diagnosis
  • prognosis
  • personalized medicine
  • molecular pathways
  • drug development targets

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Published Papers (3 papers)

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Research

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15 pages, 1193 KB  
Article
Somatostatin Receptor 2 Overexpression in Hepatocellular Carcinoma: Implications for Cancer Biology and Therapeutic Applications
by Servando Hernandez Vargas, Solmaz Aghaamiri, Jack T. Adams, Tyler M. Bateman, Belkacem Acidi, Sukhen C. Ghosh, Vahid Khalaj, Ahmed O. Kaseb, Hop S. Tran Cao, Majid Momeny and Ali Azhdarinia
Curr. Oncol. 2025, 32(9), 512; https://doi.org/10.3390/curroncol32090512 - 13 Sep 2025
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Abstract
(1) Background: Somatostatin receptor 2 (SSTR2), a G protein-coupled receptor, is overexpressed in multiple malignancies, including hepatocellular carcinoma (HCC). While SSTR2 has traditionally been viewed as an inhibitory receptor involved in suppressing hormone secretion and cell proliferation, emerging evidence suggests a more complex [...] Read more.
(1) Background: Somatostatin receptor 2 (SSTR2), a G protein-coupled receptor, is overexpressed in multiple malignancies, including hepatocellular carcinoma (HCC). While SSTR2 has traditionally been viewed as an inhibitory receptor involved in suppressing hormone secretion and cell proliferation, emerging evidence suggests a more complex role in cancer biology. However, the functional implications of SSTR2 expression in HCC remain poorly understood. This study aimed to systematically investigate the molecular landscape associated with SSTR2 expression in HCC and evaluate its potential as a therapeutic target. (2) Methods: SSTR2 expression patterns across 22 tumor types were assessed using TNMplot, and its expression in HCC was further validated through The Human Protein Atlas. Integrative analysis of transcriptomic profiles, protein expression data, and somatic copy number alterations was performed using data from The Cancer Genome Atlas (TCGA) to stratify HCC patients by SSTR2 expression levels. Gene Ontology (GO) enrichment analysis was conducted via SRplot to uncover biological processes and signaling pathways associated with SSTR2. Kaplan–Meier survival analyses were performed using GEO datasets to determine the prognostic significance of SSTR2 expression. (3) Results: SSTR2 is moderately expressed in the majority of HCC tumors. Elevated SSTR2 expression correlates with significantly poorer overall and disease-specific survival. High SSTR2 levels are associated with activation of oncogenic signaling cascades related to cell proliferation, epithelial-to-mesenchymal transition (EMT), angiogenesis, and metastasis. Additionally, SSTR2 expression is positively correlated with several receptor tyrosine kinases and oncogenes implicated in HCC progression. (4) Conclusions: Our findings suggest that SSTR2 is not merely a passive biomarker but may contribute to HCC pathogenesis through modulation of oncogenic pathways. These data support the rationale for further development of SSTR2-directed therapeutic strategies to inhibit tumor growth and invasion in HCC patients. Full article
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Review

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16 pages, 1215 KB  
Review
Understanding Chemotherapy-Induced Thrombocytopenia: Implications for Gastrointestinal Cancer Treatment
by Supriya Peshin, Adit Dharia, Ehab Takrori, Jasmeet Kaur, Kannan Thanikachalam and Renuka Iyer
Curr. Oncol. 2025, 32(8), 455; https://doi.org/10.3390/curroncol32080455 - 14 Aug 2025
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Abstract
Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates [...] Read more.
Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates of CIT. This complication often leads to treatment delays, dose reductions, and elevated bleeding risk. This review provides a comprehensive overview of the pathophysiology, clinical implications, and management strategies of CIT in GI malignancies. CIT arises from several mechanisms: direct cytotoxicity to megakaryocyte progenitors, disruption of the marrow microenvironment, thrombopoietin dysregulation, and immune-mediated platelet destruction. Platinum agents, antimetabolites, and immune checkpoint inhibitors can contribute to these effects. Oxaliplatin-induced CIT may occur acutely via immune mechanisms or chronically through marrow suppression. CIT affects 20–25% of solid tumor patients, with highest rates in those receiving gemcitabine (64%), carboplatin (58%), and oxaliplatin (50%). Within GI cancer regimens, FOLFOXIRI and S-1 plus oxaliplatin show higher CIT incidence compared to FOLFIRI and CAPIRI. Thrombocytopenia is graded by severity, from mild (Grade 1–2) to severe (Grade 3–4), and often necessitates treatment adjustments, transfusions, or supportive therapies. Current strategies include chemotherapy dose modification, platelet transfusion, and thrombopoietin receptor agonists (TPO-RAs) like romiplostim and eltrombopag. While platelet transfusions help in acute settings, TPO-RAs may preserve dose intensity and reduce bleeding. Emerging agents targeting megakaryopoiesis and marrow protection offer promising avenues for long-term management. Full article
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18 pages, 522 KB  
Review
Role of Immunotherapy in the Treatment of Hepatocellular Carcinoma
by Irina Y. Dobrosotskaya, Rashmi Kumar and Timothy L. Frankel
Curr. Oncol. 2025, 32(5), 264; https://doi.org/10.3390/curroncol32050264 - 30 Apr 2025
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Abstract
Hepatocellular carcinoma is the most common primary liver tumor and is strongly related to underlying liver cirrhosis. Common etiologies include viral hepatitis, elevated alcohol consumption and metabolic diseases, all of which result in liver inflammation and scarring. Previously, systemic therapies for locally advanced [...] Read more.
Hepatocellular carcinoma is the most common primary liver tumor and is strongly related to underlying liver cirrhosis. Common etiologies include viral hepatitis, elevated alcohol consumption and metabolic diseases, all of which result in liver inflammation and scarring. Previously, systemic therapies for locally advanced or metastatic disease were limited to tyrosine kinase inhibitors with poor efficacy and rare cures. Recent advances have harnessed the power of the immune system to combat disease, resulting in improved outcomes and occasional cures. Here, we describe the recent clinical trials in immunotherapies for the treatment of hepatocellular carcinoma as first- and second-line therapies and in combination with other drug classes. Full article
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