Emerging Therapies in the Management of Gastrointestinal Malignancies (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 3607

Special Issue Editor


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Guest Editor
Division of Surgical Oncology and Hepatopancreatobiliary Surgery, Arrowhead Regional Academic Comprehensive Cancer Center, California University of Science and Medicine, Colton, CA 92324, USA
Interests: cholangiocarcinoma; biliary malignancies; primary liver cancers; metastatic liver malignancies; minimally invasive surgery
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Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue "Emerging Therapies in the Management of Gastrointestinal Malignancies".

Gastrointestinal cancer is the leading cause of cancer-related deaths globally. In recent decades, the paradigm of management of gastrointestinal malignancies has shifted from conventional cytotoxic chemotherapy regimens with limited benefit to more selective and efficient, mechanism-based therapeutics. A better understanding of genomic profiling and molecular pathogenesis of tumors has resulted in the development of novel targeted therapies and precision medicine. Boosting host antitumor reaction via immunotherapy has also revolutionized the landscape for the treatment of some gastrointestinal cancers.

The management strategy of esophageal, gastric, and colorectal cancers has changed remarkably in the past decade, and there are promising developments in the treatment of cancers with a high fatality rate such as pancreas cancers and cholangiocarcinoma. In this Special Issue, we sincerely hope to gather experts to discuss the latest scientific developments in the field.

Dr. Amir A. Rahnemai Azar
Guest Editor

Manuscript Submission Information

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Keywords

  • hepatocellular carcinoma
  • colorectal cancer
  • esophageal cancer
  • immunotherapy
  • targeted therapy

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Published Papers (3 papers)

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Research

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11 pages, 836 KiB  
Article
Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer
by Víctor Domínguez-Prieto, Miguel León-Arellano, Rocío Olivera-Salazar, Luz Vega-Clemente, Cristina Caramés, Eva Ruiz-Hispán, Raquel Fuentes-Mateos, Diana Rosero-Rodríguez, Héctor Guadalajara, Mariano García-Arranz and Damián García-Olmo
Cancers 2025, 17(6), 965; https://doi.org/10.3390/cancers17060965 - 13 Mar 2025
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Abstract
Background and objective: Multiple markers have been proposed, but there are no reliable pre-treatment markers that predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. The objective of this study is to evaluate the usefulness of pre-treatment SEPTIN9 [...] Read more.
Background and objective: Multiple markers have been proposed, but there are no reliable pre-treatment markers that predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. The objective of this study is to evaluate the usefulness of pre-treatment SEPTIN9 gene methylation ratio as a predictor of tumor response to total neoadjuvant therapy and its correlation with tumor size and tumor stage in patients with locally advanced rectal cancer. Methods: Patients with locally advanced rectal cancer (T3/4 and/or N+ histologically confirmed rectal cancer) undergoing total neoadjuvant therapy were included. Tumor size and tumor stage were determined by magnetic resonance. SEPTIN9 gene methylation in plasmatic cfDNA was analyzed by droplet digital PCR at the time of diagnosis. After completing total neoadjuvant therapy, tumor response was assessed by magnetic resonance and proctoscopy. The correlation between pre-treatment SEPTIN9 gene methylation ratio, tumor size, tumor stage and tumor response was analyzed. Results: 39 patients with locally advanced rectal cancer were included. Pre-treatment SEPTIN9 gene methylation ratio (p = 0.033) and tumor size (p = 0.026), but not tumor stage, significantly correlated with tumor response to total neoadjuvant therapy. Pre-treatment SEPTIN9 gene methylation ratio also correlated with N stage (p = 0.040) and tumor size (p = 0.001), but not with T stage (p = 0.846). Conclusions: Pre-treatment SEPTIN9 gene methylation ratio correlates with tumor size and N stage and can predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. Full article
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20 pages, 3077 KiB  
Article
Colorectal Adenoma Subtypes Exhibit Signature Molecular Profiles: Unique Insights into the Microenvironment of Advanced Precancerous Lesions for Early Detection Applications
by Francesco Mattia Mancuso, Juan Carlos Higareda-Almaraz, Pol Canal-Noguer, Arianna Bertossi, Alexandre Perera-Lluna, Michael Herbert Alexander Roehrl and Kristi Kruusmaa
Cancers 2025, 17(4), 654; https://doi.org/10.3390/cancers17040654 - 14 Feb 2025
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Abstract
Background: Colorectal cancer (CRC) is characterized by the uncontrolled growth of malignant colonic or rectal crypt epithelium. About 85% of CRCs evolve through a stepwise progression from advanced precancerous adenoma lesions. A better understanding of the evolution from adenoma to carcinoma can [...] Read more.
Background: Colorectal cancer (CRC) is characterized by the uncontrolled growth of malignant colonic or rectal crypt epithelium. About 85% of CRCs evolve through a stepwise progression from advanced precancerous adenoma lesions. A better understanding of the evolution from adenoma to carcinoma can provide a window of opportunity not only for early detection and therapeutic intervention but potentially also for cancer prevention strategies. Methods: This study investigates the heterogeneous methylation, copy-number alteration (CNA), and mutation signals of histological adenoma subtypes in the context of progression from normal colon to advanced precancerous lesions (APLs) and early-stage CRC. Results: Differential methylation analysis revealed 2321 significantly altered regions among APLs: 137 hypermethylated regions in serrated vs. tubular, 2093 in serrated vs. tubulovillous, and 91 in tubular vs. tubulovillous adenoma subtypes. The most differentiating pathways for serrated adenomas belonged to cAMP signaling and the regulation of pluripotency of stem cells, while regions separating tubular and tubulovillous subtypes were enriched for WNT signaling. CNA events were mostly present in tubular or tubulovillous adenomas, with the most frequent signals being seen in chromosomes 7, 12, 19, and 20. In contrast, early-stage CRC exhibited signals in chromosomes 7, 8, and 20, indicating different processes between APL and early-stage CRC. Mutations reinforce subtype-level differences, showing specific alterations in each subtype. Conclusions: These findings are especially important for developing early detection or cancer prevention tests trying to capture adenoma signatures. Full article
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Review

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12 pages, 537 KiB  
Review
Current Advances in Immunotherapy Management of Esophageal Cancer
by Sagar Pyreddy, Sarah Kim, William Miyamoto, Zohray Talib, Dev A. GnanaDev and Amir A. Rahnemai-Azar
Cancers 2025, 17(5), 851; https://doi.org/10.3390/cancers17050851 - 1 Mar 2025
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Abstract
Esophageal cancer is one of the most common and deadliest cancers worldwide. Rates of esophageal cancer worldwide have been steadily rising over the past decade due to higher incidence of gastroesophageal reflux disease (GERD). Current therapies include surgical resection, chemotherapy, and limited targeted [...] Read more.
Esophageal cancer is one of the most common and deadliest cancers worldwide. Rates of esophageal cancer worldwide have been steadily rising over the past decade due to higher incidence of gastroesophageal reflux disease (GERD). Current therapies include surgical resection, chemotherapy, and limited targeted therapies. One obstacle to care is tumor cells’ ability to evade immune surveillance, which can render certain therapeutics ineffective. Immunotherapy provides a new paradigm to cancer treatment, which has proven to be effective in evasive tumors. In recent years, PD-1/PD-L1 and CLTA-4 inhibitors have been used as frontline treatment and have shown to be extremely effective in the treatment of hard-to-treat tumors. Here, we aim to analyze the current literature regarding current therapeutics along with emerging techniques and future receptor targets for immunotherapy. Full article
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