Submit to Special Issue Submit Abstract to Special Issue Review for Cells Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 22297

Share This Special Issue

Special Issue Editors

Dr. Federica Laudisi

E-Mail Website
Guest Editor

Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal cancer; inflammatory bowel disease; intestinal inflammation; intestinal epithelial barrier; microbiota; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Dr. Carmine Stolfi

E-Mail Website
Guest Editor

Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal cancer; immunotherapy; inflammatory bowel diseases; anti-cancer drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastrointestinal cancer includes all cancers arising in the digestive tract organs, such as esophageal and gastric cancers, hepatobiliary cancers, pancreatic cancers, and colorectal cancers. When combined together, gastrointestinal cancers account for more new cases and deaths per year than cancers occurring in any other system of the body, and their incidence continues to increase. Additionally, in most cases, these malignancies are diagnosed at an advanced stage, leading to a poor prognosis despite the availability of different therapeutic approaches (e.g., chemotherapy, immunotherapy, radiotherapy). Even in patients with potentially curative cancer, almost half of them will develop recurrent disease. Despite recent technological advances and major scientific efforts, the cellular and molecular pathways that underpin the pathogenesis and progression of these malignancies are still being uncovered. Better knowledge of these mechanisms can definitely improve our understanding of gastrointestinal cancer cell biology and offer opportunities for the design of new and more effective therapeutic strategies.

In this Special Issue, we invite scholars working on gastrointestinal cancer to submit original research papers or review articles dealing with novel mechanistic insights and details of the molecular signatures of oncogenic transformation and disease progression. We also encourage the submission of manuscripts that focus on translating basic molecular knowledge to new medical applications. Articles focusing on diagnostic and prognostic biomarkers, as well as novel drug targets or targeted treatments, including possible clinical trials, are also welcomed.

Dr. Federica Laudisi
Dr. Carmine Stolfi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

colorectal cancer
gastric cancer
liver cancer
pancreatic cancer
tumor microenvironment
cytokines
epigenetic
checkpoint inhibitors
biomarkers
immunotherapy

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (11 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

17 pages, 4162 KB

Open AccessArticle

Rapid Drug Sensitivity Profiling via a Novel High-Success-Rate Culture Method for Patient-Derived Pancreatic Cancer: An Exploratory Preclinical Platform for Advancing Clinical Applications and Drug Development

by Yu Kato, Naoki Yamamoto, Yuichiro Uchida, Noriko Hiramatsu, Takato Ozeki, Yukari Minobe, Yukika Hasegawa, Sho Kawabe, Hikaru Yabuuchi, Seiji Yamada, Yuko Hata, Eiji Sugihara, Tetsuya Takimoto, Kuniaki Saito, Takeshi Takahara, Koichi Suda, Osamu Nagano and Hideyuki Saya

Cells 2026, 15(4), 313; https://doi.org/10.3390/cells15040313 - 7 Feb 2026

Viewed by 573

Abstract

Pancreatic cancer is a highly intractable malignancy that necessitates personalized treatment strategies. Conventional patient-derived models, such as three-dimensional organoids, are often limited by intellectual property constraints and high costs. In this study, we developed an affordable adherent culture system for patient-derived pancreatic cancer cells using a proprietary medium and laminin-coated dishes. Primary cultures were successfully established from 28 patients with pancreatic ductal adenocarcinoma, exceeding a 90% success rate. Validation of eight samples confirmed maintenance of epithelial cell adhesion molecule expression and preservation of oncogenic KRAS mutations. Transcriptomic profiling revealed consistent upregulation of a six-gene signature (FAP, IGFBP5, PRRX1, SPARC, WNT5A, and ADAMTS12), which is associated with malignancy. In vitro drug sensitivity assays revealed interpatient heterogeneity with preliminary clinical associations. In conclusion, this simplified platform provides high-purity cancer cells and serves as a functional precision medicine tool. Beyond conventional chemotherapy, this platform has the potential to support applications ranging from biomarker validation and exploratory preclinical testing of novel therapeutics, including immune checkpoint inhibitors and antibody–drug conjugates. This optimization can lead to personalized therapeutic strategies for pancreatic cancer. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

17 pages, 1818 KB

Open AccessArticle

Targeting the c-Met/VEGFR Pathway to Boost Nab-Paclitaxel Efficacy in Gastric Cancer: Preclinical Insights

by Jennifer Huang, Quinn Kaurich, Md Sazzad Hassan, Urs von Holzen and Niranjan Awasthi

Cells 2026, 15(3), 285; https://doi.org/10.3390/cells15030285 - 3 Feb 2026

Viewed by 530

Abstract

Combination chemotherapy regimens are commonly employed to treat advanced gastric adenocarcinoma (GAC), yet median survival remains less than one year. Nab-paclitaxel has demonstrated significant antitumor activity in preclinical GAC models. Overexpression of growth factors and their receptors is prevalent in GAC and contributes to its pathophysiology, with aberrant activation of the HGF/c-Met pathway reported in up to 50% of patients. We hypothesized that merestinib, a small-molecule inhibitor of c-Met, Axl, and DDR1/2, would enhance the therapeutic response to nab-paclitaxel in GAC. In high c-Met–expressing MKN-45 peritoneal dissemination xenografts in female NOD/SCID mouse models, animal survival was 17 days in controls, 37 days with nab-paclitaxel (118% increase), 24 days with merestinib (41% increase), and 43 days with the combination (153% increase), demonstrating significantly enhanced survival compared with either monotherapy. In MKN-45 subcutaneous xenografts, tumor volumes in the control, nab-paclitaxel, merestinib, and combination groups were 503 mm³, 115 mm³, 91 mm³, and −9.7 mm³ (indicating tumor regression), respectively. In low c-Met-expressing SNU-1 xenografts, tumor volumes were 219 mm³, 105 mm³, 131 mm³, and 57 mm³, respectively. IHC analysis of tumor cell proliferation and microvessel density in MKN-45 tumors supported these findings. In vitro, nab-paclitaxel and merestinib each reduced cell proliferation in GAC-associated cells, with enhanced inhibitory effects when used in combination. In MKN-45 cells, merestinib increased the expression of pro-apoptotic proteins and decreased phosphorylation of c-Met, EGFR, IGF-1R, ERK, and AKT. These results indicate that combining merestinib with nab-paclitaxel may represent a promising therapeutic strategy to improve outcomes for patients with GAC. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

16 pages, 2600 KB

Open AccessArticle

Comprehensive Characterization of the Immune Microenvironment of Colorectal and Gastric Signet Ring Cell Cancer

by Jianqing Zhang, Robin Collingwood, Sameer Al Diffalha, Deborah Della Manna, Ravi Kumar Paluri, Haider A. Mejbel and Olumide Gbolahan

Cells 2026, 15(1), 30; https://doi.org/10.3390/cells15010030 - 23 Dec 2025

Viewed by 671

Abstract

The reasons for the aggressive clinical phenotype of signet ring cell carcinoma (SRCC) have not been fully elucidated. Previous studies suggest similarities in the genotype of colorectal and gastric SRCC and a clear distinction from non-SRCC. The immune microenvironments of gastric and colorectal SRCC have not been comprehensively examined. We isolated RNA from formalin-fixed, paraffin-embedded (FFPE) sections of 34 tumor specimens, 10 colorectal SRCC, 24 gastric SRCC, 4 non-SRCC colorectal (CCC), and 3 gastric adenocarcinoma (GCC) samples. The PanCancer Immune Profiling Panel was used to evaluate the expression of 770 immune-related genes. We compared the expression profiles of colorectal and gastric SRCC and non-SRCC adenocarcinoma. We found that the immune-related gene expression profiles (GEPs) of colorectal SRCC (CR-SRCC) and gastric SRCC (G-SRCC) were distinct from the non-SRCC. A total of 127 genes were upregulated and 32 downregulated in CR-SRCC compared to CCC. Only two genes (CCL27 and LAIR2 reached statistical significance (p-adj < 0.05)) among the differentially expressed genes in G-SRCC compared to GCC. None of the clinically relevant immune checkpoints were significantly differentially expressed in SRCC vs. non-SRCC. Overall, we noted a relative abundance of CD8+ cells in CR-SRCC and G-SRCC and relative overexpression of genes involved in innate immune response including the complement pathway. Finally, we identified IL13RA2 as a potential biomarker and therapeutic target candidate for CR-SRCC. The immune microenvironments of CR-SRCC and G-SRCC are distinct from non-SRCC. Broadly, both CR-SRCC and G-SRCC are characterized by a complex immune microenvironment that features cytotoxic cells and innate immune activity that may facilitate immune evasion. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

17 pages, 2609 KB

Open AccessArticle

Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer

by Hajime Matsuida, Kosaku Mimura, Shotaro Nakajima, Katsuharu Saito, Sohei Hayashishita, Chiaki Takiguchi, Azuma Nirei, Tomohiro Kikuchi, Hiroyuki Hanayama, Hirokazu Okayama, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze and Koji Kono

Cells 2025, 14(15), 1212; https://doi.org/10.3390/cells14151212 - 6 Aug 2025

Viewed by 1279

Abstract

Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

Review

Jump to: Research

23 pages, 1552 KB

Open AccessReview

Translating Gastric Cancer Genomics into Targeted Therapy: Mechanistic Insights from Animal Models and Patient-Derived Systems

by Rong-Yaun Shyu, Lu-Kai Wang and Fu-Ming Tsai

Cells 2026, 15(4), 365; https://doi.org/10.3390/cells15040365 - 18 Feb 2026

Viewed by 648

Abstract

Gastric cancer remains a leading cause of cancer-related mortality worldwide and is marked by pronounced molecular heterogeneity. Advances in genomic profiling have identified key genetic alterations, including oncogenes (HER2, PIK3CA, and MYC), tumor suppressor genes (TP53, CDH1, and ARID1A), and regulators of genome stability and cell architecture (MLH1, RHOA, and CLDN18), which have driven the development of targeted therapeutic strategies. Although genetically engineered mouse models and xenograft systems have been indispensable for functional validation and preclinical drug testing, many approaches that showed promising efficacy in animal models—such as inhibition of EGFR, MET, FGFR2, and the PI3K pathway—failed to translate into overall survival benefits in clinical trials, highlighting major translational limitations. In contrast, HER2- and CLDN18.2-targeted therapies represent rare but notable clinical successes, underscoring the importance of true oncogenic dependency, precise biomarker-driven patient selection, and robust preclinical validation. In this review, we systematically categorize gastric cancer-associated genes according to their biological functions, summarize representative animal models, and critically examine key successes and failures in clinical translation, emphasizing the need for biologically faithful models and precision-driven translational strategies. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

34 pages, 1894 KB

Open AccessReview

Oncolytic Virotherapy in Colorectal Cancer: Mechanistic Insights, Enhancer Strategies, and Translational Combinations

by Huda Salameh, Nesha Naseem, Muhammad A. Chattha, Joytish Ramesh, Haneen Ramy, Dasa Cizkova, Peter Kubatka and Dietrich Büsselberg

Cells 2025, 14(24), 2006; https://doi.org/10.3390/cells14242006 - 16 Dec 2025

Viewed by 935

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, with most patients, especially those with microsatellite-stable disease, having limited treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic modality due to their ability to selectively replicate in malignant cells and mediate antitumor effects through direct oncolysis, immune activation, and modulation of tumor angiogenesis. This review analyzed 101 primary studies that reported the use of OV in CRC. The extracted data, including virus type, study design, model system, mechanistic pathways, and therapeutic strategies, were organized as standalone therapy, combination therapy, or enhancer-based approaches. Across studies, OV monotherapy consistently induced selective tumor cell lysis and, in some models, also exhibited additional immunogenic and anti-angiogenic effects. Combination strategies, particularly those with immune checkpoint inhibitors, demonstrated synergistic activity, enhancing T-cell infiltration, cytokine production, and tumor control even in resistant CRC settings. Enhancer approaches, including mesenchymal stem cell delivery systems and tumor-specific promoters, have improved viral selectivity, tumor penetration, and reduced immune clearance. Despite promising findings, progress is hindered by heterogeneous models and the scarcity of advanced clinical trials. Translation into well-designed clinical studies is now warranted to optimize therapeutic outcomes. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Graphical abstract

22 pages, 649 KB

Open AccessReview

Targeting Cancer Cell Energy Metabolism in Colorectal Cancer: Opportunities and Challenges from Drug Repositioning

by Lorenzo Tomassini, Teresa Pacifico, Giovanni Monteleone, Carmine Stolfi and Federica Laudisi

Cells 2025, 14(24), 1968; https://doi.org/10.3390/cells14241968 - 11 Dec 2025

Viewed by 1152

Abstract

Drug repositioning, also known as drug repurposing, represents a cost-effective and time-efficient approach to accelerate the development of novel therapies for colorectal cancer (CRC), the third most common cancer worldwide, with an estimated two million new cases and nearly one million deaths annually. This review aims to critically evaluate how existing non-oncologic drugs can be repositioned to exploit key metabolic vulnerabilities of CRC cells. Targeting cancer cell metabolism offers a unique therapeutic advantage, as it disrupts the bioenergetic and biosynthetic processes that sustain tumor growth, adaptation, and resistance to therapy. Specifically, we examine the mechanisms through which antidiabetic, cardiovascular, anti-inflammatory, antidepressant, and anthelmintic agents interfere with glycolysis, oxidative phosphorylation (OxPhos), and mitochondrial bioenergetics—metabolic circuits central to CRC progression and recurrence. By integrating recent mechanistic, preclinical, and clinical findings, we highlight how these repurposed drugs converge on major metabolic regulators, including the AMPK/mTOR signaling pathways, and how they can potentiate the efficacy of standard chemotherapies and immunotherapies. Furthermore, we discuss the translational challenges that must be addressed to move these compounds into clinical use. Collectively, this review underscores the therapeutic potential of targeting CRC metabolism through drug repositioning as a promising avenue toward more effective and personalized treatment strategies. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

29 pages, 2779 KB

Open AccessReview

The Two-Way Role of Jagged1 in Cancer: A Focus on CRC

by Sabrina Zema, Francesca Di Fazio, Rocco Palermo, Claudio Talora and Diana Bellavia

Cells 2025, 14(22), 1815; https://doi.org/10.3390/cells14221815 - 19 Nov 2025

Viewed by 1341

Abstract

Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies. Accumulating genetic evidence supports a multistep model of tumor progression, in which early APC loss leads to chromosomal instability and adenoma formation, followed by activating mutations in KRAS that synergize with β-catenin signaling to promote tumor growth and invasion. Among the downstream effectors of these pathways, the Notch ligand Jagged1 has emerged as a critical mediator of CRC progression and chemoresistance. Jagged1 is not only a transcriptional target of the Wnt/β-catenin axis but also undergoes proteolytic cleavage via the KRAS/ERK/ADAM17 signaling cascade, generating a nuclear Jagged1 intracellular domain (Jag1-ICD) that drives reverse signaling. This dual functionality, activating canonical Notch signaling and initiating reverse nuclear signaling, positions Jagged1 as a key oncogenic driver in CRC. In this review, we first summarize the role of Jagged1 as an integral part of canonical Notch signaling. We then focus on the non-canonical Jagged1 reverse signaling function in cancer, with a particular emphasis on CRC. We underscore the dual role of Jagged1 in tumor biology and propose that it functions as a novel oncogene within the adenoma-to-carcinoma sequence, supporting CRC development and drug resistance via non-canonical mechanisms. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Graphical abstract

16 pages, 682 KB

Open AccessFeature PaperReview

Claudin18.2 as a Promising Therapeutic Target in Gastric Cancer

by Agata Poniewierska-Baran, Paulina Plewa, Zuzanna Żabicka and Andrzej Pawlik

Cells 2025, 14(16), 1285; https://doi.org/10.3390/cells14161285 - 19 Aug 2025

Cited by 5 | Viewed by 6415

Abstract

Claudin-18.2 (CLDN18.2) is an isoform of a tight junction protein and has emerged as a promising therapeutic target in gastric cancer (GC). CLDN18.2 is responsible for gastric homeostasis and protects epithelial cells from low pH conditions. Interestingly, CLDN18.2 expression is strictly restricted to the stomach, making it an ideal tumor marker. This narrative review presents the characterization and role of claudin 18.2 (CLDN18.2) as a promising biomarker in GC and a target for clinical therapies, more specifically CLDN18.2-targeted drugs and therapies including mABs (e.g., Zolbetuximab, Osemitamab, ZL-1211), bsAB, and CAR-T cell-based immunotherapies. We also summarize numerous ongoing worldwide clinical trials that are evaluating CLDN18.2 as a target for GC treatment. What seems to be crucial is that preclinical and clinical data indicate their high efficacy and safety. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

16 pages, 716 KB

Open AccessReview

Unconventional T Cells’ Role in Cancer: Unlocking Their Hidden Potential to Guide Tumor Immunity and Therapy

by Paola Pinco and Federica Facciotti

Cells 2025, 14(10), 720; https://doi.org/10.3390/cells14100720 - 15 May 2025

Cited by 4 | Viewed by 2821

Abstract

Unconventional T (UC T) cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, γδ T cells, and double-negative (DN) T cells, are key players in immune surveillance and response due to their properties combining innate-like and adaptive-like features. These cells are widely present in mucosal tissues, where they can rapidly respond to infections and tumor-associated changes. In fact, UC T cells can have both pro- and anti-tumoral effects, with their activity influenced by factors such as microbial composition and the tumor microenvironment. In particular, intratumoral microbiota significantly impacts the development, function, and activation of UC T cells, influencing cytokine production and shaping the immune response in various cancers. The complex crosstalk between UC T cells and the surrounding factors is discussed in this review, with a focus on how these cells might be interesting candidates to explore and exploit as anticancer therapeutic agents. However, the great potential of UC T cells, not only demonstrated in the context of adoptive cell transfer, but also enhanced through techniques of engineering, is still flanked by different challenges, like the immunosuppressive tumor microenvironment and heterogeneity of target molecules associated with some specific categories of tumors, like gastrointestinal cancers. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Figure 1

30 pages, 1092 KB

Open AccessReview

B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature

by Sylwia Mielcarska, Anna Kot, Agnieszka Kula, Miriam Dawidowicz, Piotr Sobków, Daria Kłaczka, Dariusz Waniczek and Elżbieta Świętochowska

Cells 2025, 14(7), 530; https://doi.org/10.3390/cells14070530 - 2 Apr 2025

Cited by 5 | Viewed by 4763

Abstract

B7-H3 (CD276), a member of the B7 immune checkpoint family, plays a critical role in modulating immune responses and has emerged as a promising target in cancer therapy. It is highly expressed in various malignancies, where it promotes tumor evasion from T cell surveillance and contributes to cancer progression, metastasis, and therapeutic resistance, showing a correlation with the poor prognosis of patients. Although its receptors were not fully identified, B7-H3 signaling involves key intracellular pathways, including JAK/STAT, NF-κB, PI3K/Akt, and MAPK, driving processes crucial for supporting tumor growth such as cell proliferation, invasion, and apoptosis inhibition. Beyond immune modulation, B7-H3 influences cancer cell metabolism, angiogenesis, and epithelial-to-mesenchymal transition, further exacerbating tumor aggressiveness. The development of B7-H3-targeting therapies, including monoclonal antibodies, antibody–drug conjugates, and CAR-T cells, offers promising avenues for treatment. This review provides an up-to-date summary of the B7H3 mechanisms of action, putative receptors, and ongoing clinical trials evaluating therapies targeting B7H3, focusing on the molecule’s role in gastrointestinal tumors. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)

► Show Figures

Journal Menu

Journal Browser

Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (11 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI