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Cancers
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Novel Approaches to the Management of Patients with Gastrointestinal Tumors
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Novel Approaches to the Management of Patients with Gastrointestinal Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (15 March 2026) | Viewed by 8935

Editors

Dr. Javier Rodriguez

E-Mail Website
Guest Editor
Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, 31008 Navarra, Spain
Interests: gastrointestinal oncology; gastric cancer; colorectal cancer; pancreatic cancer; immunotherapy; clinical trials; neuroendocrine tumors
Special Issues, Collections and Topics in MDPI journals
Dr. Ignacio Matos García

E-Mail Website
Guest Editor
Department of Medical Oncology, Gastrointestinal Unit, Cancer Center Clínica Universidad de Navarra, Madrid, Spain
Interests: gastrointestinal oncology; gastric cancer; colorectal cancer; immunotherapy; phase I clinical trials; neuroendocrine tumors; early drug development

Special Issue Information

Dear Colleagues,

Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of cancer deaths annually. Although surgical resection remains the most common curative treatment for digestive cancers, the introduction of multimodal therapeutic approaches has improved the survival of many of these tumors. In addition, significant advancements in our understanding of the molecular biology underlying these tumors, including the interplay between cancer cells and the surrounding cancer microenvironment, have provided novel therapeutic alternatives and unprecedented insights into the genetic drivers of tumor progression, the mechanisms of therapy resistance, the role of targeted therapies, especially immunotherapy, and the key role of cfDNA in providing prognostic information. This knowledge is continuously translated into novel treatment concepts and targets, which are transforming the therapeutic landscape of these tumors. In this Special Issue, we will focus on novel approaches to the management of patients with esophageal, gastric, and colorectal cancers. This may include TNT approaches, the pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy, innovative therapeutic strategies such as CAR-T cell therapy or novel antibody-drug conjugates, and the impact of artificial intelligence, the microbiome or omics on the design of alternative strategies.

Dr. Javier Rodríguez
Dr. Ignacio Matos García
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 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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers 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 2900 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

  • clinical management
  • gastric cancer
  • colorectal cancer
  • predictive factors
  • novel therapies
  • artificial intelligence

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Published Papers (4 papers)

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Research

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15 pages, 606 KB  
Article
Do All Stage IA Pancreatic Cancer Patients Need Adjuvant Chemotherapy?
by John M. Lyons III, Mei-Chin Hsieh, Kenneth C. Avanzino, Mohammad Al Efishat and Quyen Chu
Cancers 2026, 18(8), 1195; https://doi.org/10.3390/cancers18081195 - 8 Apr 2026
Viewed by 862
Abstract
Background: National guidelines recommend adjuvant chemotherapy (AC) following resection for all stages of pancreatic cancer (PDAC), but the benefit of AC in Stage IA disease remains unclear. The objective of this study was to identify a subgroup of patients with Stage IA PDAC [...] Read more.
Background: National guidelines recommend adjuvant chemotherapy (AC) following resection for all stages of pancreatic cancer (PDAC), but the benefit of AC in Stage IA disease remains unclear. The objective of this study was to identify a subgroup of patients with Stage IA PDAC that could possibly forego AC. Study Design: The National Cancer Database (NCDB) was queried to identify all patients with Stage IA PDAC diagnosed from 2010 to 2021. Patients who received AC were compared to those who did not. Multivariable analysis was conducted to identify risk factors associated with overall survival (OS). Results: There were 1421 patients eligible for analysis. On multivariable analysis, we found nine factors associated with worse overall OS: advanced age (p = 0.0414), lower median income (p = 0.0148), Medicare (p = 0.0180), higher-grade tumor histology (p = 0.0182), LVI (p = 0.0028), positive surgical margins (p = 0.0027), examination of fewer than 12 lymph nodes (p = 0.0395), and a length of stay greater than 7 days (p < 0.0001). OS was negatively correlated with an increased number of risk factors. Improved OS was observed following AC in patients with three (∆OS = +54 months; p = 0.0016) or four or more risk factors (∆OS = +11.4 months; p = 0.0250). However, patients with fewer than three risk factors did not experience improvement in OS following AC. Conclusions: AC does not appear to benefit Stage IA PDAC patients with fewer than three risk factors indicating that it may be safe to omit AC in these individuals. Full article
(This article belongs to the Special Issue Novel Approaches to the Management of Patients with Gastrointestinal Tumors)
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28 pages, 5673 KB  
Article
Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer
by Mahadi Hasan, Morgan Eikanger, Sanam Sane, Krishantha S. K. Wijewardhane, John L. Slunecka, Jessica Freeling, Khosrow Rezvani and Grigoriy Sereda
Cancers 2025, 17(19), 3253; https://doi.org/10.3390/cancers17193253 - 8 Oct 2025
Cited by 3 | Viewed by 1999
Abstract
Background: Despite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors. This study revealed the apoptotic and anti-growth mechanism of VTD, a previously used anti-hypertensive supplement, can elevate [...] Read more.
Background: Despite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors. This study revealed the apoptotic and anti-growth mechanism of VTD, a previously used anti-hypertensive supplement, can elevate UBXN2A, a known tumor suppressor protein in CRC, and simultaneously enhance intrinsic and extrinsic apoptosis in metastatic cancer cells. Methods and Results: An AOM/DSS mouse model of CRC showed that UBXN2A haplosufficient (UBXN2A +/−) mice treated with VTD had less tumor burden than mice with the full UBXN2A gene treated with vehicle. We have previously shown that casein-coated mesoporous silica nanoparticles (MSNs) offer an effective local delivery of drugs at tumor sites. Our findings demonstrate that the high rate of extracellular release of matrix metalloproteinases (MMPs), particularly MMP-7, by metastatic colon cancer cells, triggers the release of VTD from casein-coated mesoporous MSNs. This shows the “Zip Code” mechanism for the local enrichment of VTD at the tumor sites. After in vitro drug release verification, two independent mouse experiments, a xenograft and a splenolepatic metastatic mouse model of CRC, were used to evaluate the therapeutic efficacy of VTD-loaded and casein-coated carboxylated mesoporous silica nanoparticles, MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg). Animal experiments revealed that MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg) slows down the progress of tumors. Mass spectrometry (MS) revealed improved pharmacokinetics (PK) profile as MSN-COOH/VTD/CAS had less VTD accumulation in non-cancerous organs compared to pure VTD. We further improved nanoparticle targeting and drug release by shifting to calcium-based particles (CBPs). The engineered CBPs demonstrated higher drug-releasing performance. Without the MMPs trigger, MSNs show slow and continuous “drug leak” over longer period of time whereas CCSMPs stops leakage within an hour. Additionally, CBPs showed higher sensitivity to MMP-7 than MMP-9, enhancing the targetability of CBPs for CRC metastatic tumors with excessive extracellular MMP-7. Conclusions: This study introduces a new platform utilizing nanoparticle-based site-specific delivery of a plant-based anti-metastatic molecule, veratridine, with enhanced safety and therapeutic efficacy for the treatment of metastatic CRC. Full article
(This article belongs to the Special Issue Novel Approaches to the Management of Patients with Gastrointestinal Tumors)
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16 pages, 570 KB  
Article
Neoadjuvant Chemoradiotherapy in Locally Advanced Gastric Adenocarcinoma: Long-Term Results and Statistical Algorithm to Predict Individual Risk of Relapse
by Miguel Ortego, Olast Arrizibita, Adriana Martinez-Lage, Ángel Vizcay Atienza, Laura Álvarez Gigli, Oskitz Ruiz, José Carlos Subtil, Maialen Zabalza, Victor Valentí, Ana Tortajada, María José Hidalgo, Onintza Sayar and Javier Rodriguez
Cancers 2025, 17(9), 1530; https://doi.org/10.3390/cancers17091530 - 30 Apr 2025
Cited by 2 | Viewed by 2283
Abstract
Background: The purpose of this study was to evaluate the long-term outcomes of patients with locally advanced gastric adenocarcinoma (LAGC) intended to receive induction chemotherapy, chemoradiation and surgery and to develop an algorithm to estimate the individual risk of relapse in a population-based [...] Read more.
Background: The purpose of this study was to evaluate the long-term outcomes of patients with locally advanced gastric adenocarcinoma (LAGC) intended to receive induction chemotherapy, chemoradiation and surgery and to develop an algorithm to estimate the individual risk of relapse in a population-based setting. Methods: Patients with LAGC (cT3-4 and/or N+) were retrospectively evaluated. A pathological response was graded according to the Becker criteria. The nodal regression grade was assessed by a 4-point scale (A–D). A comprehensive analysis of 155 individual patient variables was performed, and logistic regression (LR) was utilized to develop a predictive model for relapse risk. Results: From 2010 to 2024, 48 patients were analyzed. After a median follow-up of 49 months (range, 12–212), the 5-year actuarial PFS and OS rates were 44% and 48%, respectively. Four variables were identified as the most relevant features for training the LR model. Scores for the model accuracy, sensitivity and specificity (mean +/− sd) were 0.79 +/− 0.12, 0.74 +/− 0.221 and 0.88 +/− 0.14, respectively. For a validation dataset, the figures were 0.78, 0.88 and 0.73, respectively. Conclusions: This neoadjuvant strategy seems to correlate with a favorable long-term outcome in a subset of intestinal-type LAGA patients who achieve ypN0 features. Full article
(This article belongs to the Special Issue Novel Approaches to the Management of Patients with Gastrointestinal Tumors)
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Review

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22 pages, 681 KB  
Review
Immune-Checkpoint Inhibitors for Biliary Tract Cancer: Who Benefits and What Is Next?
by Lucía Ceniceros, Manuel de La Torre, Ana Landa Magdalena, Paloma Sangro, Josepmaria Argemí, Delia D’Avola, Bruno Sangro and Mariano Ponz-Sarvisé
Cancers 2025, 17(17), 2811; https://doi.org/10.3390/cancers17172811 - 28 Aug 2025
Cited by 4 | Viewed by 3203
Abstract
Biliary tract cancer (BTC) is a rare and aggressive type of malignancy characterized by heterogeneity both in tumor biology and in the immune microenvironment. Most patients are diagnosed with advanced-stage disease and have limited curative options. Although the introduction of immune-checkpoint inhibitors (ICI) [...] Read more.
Biliary tract cancer (BTC) is a rare and aggressive type of malignancy characterized by heterogeneity both in tumor biology and in the immune microenvironment. Most patients are diagnosed with advanced-stage disease and have limited curative options. Although the introduction of immune-checkpoint inhibitors (ICI) has transformed the treatment landscape for several solid tumors, their effects on BTC remain modest. New combinations have promoted incremental improvements in the survival of patients with advanced BTC, but the complex interplay between immune therapies and the tumor microenvironment continues to be a major challenge to improve therapeutic outcomes. Nonetheless, ongoing studies are investigating combinations that may potentially improve results in this lethal disease. This review provides an overview of the evolving role of ICIs in BTC, discusses the impact of tumor heterogeneity on treatment response, and explores future directions to optimize patient selection. Full article
(This article belongs to the Special Issue Novel Approaches to the Management of Patients with Gastrointestinal Tumors)
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