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Colorectal Cancers: New Approach to Their Pathology, Diagnosis and Therapy
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Colorectal Cancers: New Approach to Their Pathology, Diagnosis and Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 5263

Special Issue Editor

Dr. Mariusz Chabowski

E-Mail Website
Guest Editor
Department of Surgical Clinical Sciences, Faculty of Medicine, Wroclaw University of Science and Technology, Wroclaw, Poland
Interests: colorectal cancers; thymoma; pulmonary medicine; malignant pleural effusion; video-assisted thoracic surgery; mesothelioma; transthoracic biopsy; bronchoscopy; cancer malnutrition; dietary intervention
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the third most prevalent cancer in Poland, with its incidence increasing. Its progression typically spans several years, and its early warning signs encompass rectal bleeding, changes in bowel habits, and abdominal pain. Numerous risk factors for CRC can be mitigated through lifestyle modifications, and regular fecal occult blood tests and decennial colonoscopies have been shown to effectively reduce the incidence and mortality rates of CRC. In addition, advances in surgical techniques and the introduction of novel oncological drugs have enhanced the quality of life of patients and boosted their survival rates. Thorough preoperative preparations are crucial for minimizing complications and optimizing surgical outcomes. CRC patients are also at a higher risk of developing anxiety and depression.

This Special Issue welcomes original research papers, authoritative and up-to-date reviews, and commentaries on the following topics:

  • Novel drugs and surgical techniques for therapy against colorectal disease.
  • Molecular mechanisms of anti-colorectal cancer or cancer-preventive drugs.
  • In vitro, in vivo, and clinical studies related to colorectal cancer.
  • The usage of surgical methods in conjunction with chemotherapeutic drugs.
  • Challenges and innovative approaches to anti-colorectal cancer drug development.
  • Novel strategies for colorectal cancer prevention and intervention.
  • The production of anti-colorectal cancer agents using biotechnology.
  • Pharmacokinetic and pharmacogenomic studies on anti-colorectal cancer drugs.

Dr. Mariusz Chabowski
Guest Editor

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Keywords

  • occult blood test
  • colorectal cancer
  • colonoscopy
  • rectal bleeding
  • abdominal pain
  • hemicolectomy
  • novel oncological drugs

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Published Papers (4 papers)

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Research

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16 pages, 2627 KB  
Article
Single-Cell Mapping Reveals MIF-Centered Immunoregulatory Networks in Colorectal Cancer
by Marios Gkoris, Ilias Georgakopoulos-Soares and Apostolos Zaravinos
Int. J. Mol. Sci. 2026, 27(3), 1496; https://doi.org/10.3390/ijms27031496 - 3 Feb 2026
Viewed by 726
Abstract
Colorectal cancer (CRC) progression is strongly shaped by the tumor microenvironment (TME), where complex interactions between epithelial, immune, and stromal cells orchestrate immune suppression and tumor evolution. To dissect these relationships at single-cell resolution, we analyzed CRC scRNA-seq datasets using Seurat for data [...] Read more.
Colorectal cancer (CRC) progression is strongly shaped by the tumor microenvironment (TME), where complex interactions between epithelial, immune, and stromal cells orchestrate immune suppression and tumor evolution. To dissect these relationships at single-cell resolution, we analyzed CRC scRNA-seq datasets using Seurat for data integration and CellChat for ligand–receptor inference. We identified extensive cellular heterogeneity within the TME, dominated by CMS2/CMS3 epithelial states, SPP1+ tumor-associated macrophages, diverse T-cell subsets, and CXCR4+ B cells. Communication analysis revealed MIF-centered signaling—including MIF–CD74–CXCR4 and MIF–CD74–CD44—as the predominant axis linking tumor epithelial cells with T cells, B cells, and macrophage subpopulations. CMS3 epithelial cells displayed particularly strong connectivity to SPP1+ macrophages and cytotoxic lymphocytes through both MIF- and APP–CD74-mediated pathways. Differential gene expression confirmed elevated levels of MIF, CD74, CD44, and SPP1 in tumor tissues, while pathway enrichment analyses highlighted cytokine signaling, antigen presentation, and chemokine-regulated immune modulation as key biological processes. Collectively, our study provides a high-resolution map of CRC intercellular communication and identifies MIF-CD74-associated signaling as a central immunoregulatory hub with potential relevance for therapeutic targeting and biomarker development. Full article
(This article belongs to the Special Issue Colorectal Cancers: New Approach to Their Pathology, Diagnosis and Therapy)
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24 pages, 3580 KB  
Article
SIAH2–WNK1 Signaling Drives Glycolytic Metabolism and Therapeutic Resistance in Colorectal Cancer
by Kee-Thai Kiu, Cheng-Ying Chu, Yi-Chiao Cheng, Min-Hsuan Yen, Ying-Wei Chen, Narpati Wesa Pikatan, Vijesh Kumar Yadav and Tung-Cheng Chang
Int. J. Mol. Sci. 2026, 27(2), 1065; https://doi.org/10.3390/ijms27021065 - 21 Jan 2026
Viewed by 638
Abstract
Colorectal cancer (CRC) progression and therapy resistance are driven in part by metabolic reprogramming and the persistence of cancer stem-like cells (CSCs). The seven in absentia homolog 2 (SIAH2)/with-no-lysine kinase 1 (WNK1) signaling axis has emerged as a potential regulator of these processes, [...] Read more.
Colorectal cancer (CRC) progression and therapy resistance are driven in part by metabolic reprogramming and the persistence of cancer stem-like cells (CSCs). The seven in absentia homolog 2 (SIAH2)/with-no-lysine kinase 1 (WNK1) signaling axis has emerged as a potential regulator of these processes, yet its functional role in CRC metabolism and tumor–stroma crosstalk remains incompletely understood. Integrated analyses of The Cancer Genome Atlas–Colon Adenocarcinoma (TCGA-COAD) and Gene Expression Omnibus (GEO, GSE17538) datasets revealed significant upregulation of SIAH2 and WNK1 in CRC tissues, with strong positive correlations to glycolysis- and hypoxia-associated genes, including PFKP, LDHA, BPGM, ADH1A, ADH1B, and HIF-1α. Single-cell and clinical profiling further demonstrated preferential enrichment of SIAH2 in undifferentiated, stem-like tumor cell populations. Functional studies across multiple CRC cell lines showed that SIAH2 silencing suppressed proliferation, clonogenic growth, tumor sphere formation, and cell-cycle progression, whereas SIAH2 overexpression exerted opposite effects. Seahorse extracellular flux analyses established that SIAH2 promotes glycolytic capacity and metabolic flexibility. At the protein level, SIAH2 regulated glycolytic enzymes and WNK1/hypoxia-inducible factor-1α (HIF-1α) signaling, effects that were amplified by cancer-associated fibroblast (CAF)-derived conditioned medium. CAF exposure enhanced SIAH2 expression, CSC spheroid growth, and resistance to fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy, whereas SIAH2 depletion effectively abrogated these effects. Collectively, these findings identify the SIAH2/WNK1 axis as a central metabolic regulator linking glycolysis, CSC maintenance, and microenvironment-driven therapy resistance in CRC, highlighting its potential as a therapeutic target. Full article
(This article belongs to the Special Issue Colorectal Cancers: New Approach to Their Pathology, Diagnosis and Therapy)
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23 pages, 4922 KB  
Article
Robot-Assisted Colorectal Cancer Surgery Mitigates Early Postoperative Immunosuppression and Angiogenesis
by Mariusz G. Fleszar, Marek Zawadzki, Paulina Fortuna, Iwona Bednarz-Misa, Izabela Krauze, Kamila Maciejewska, Jakub Klekowski, Mariusz Chabowski, Wojciech Witkiewicz and Małgorzata Krzystek-Korpacka
Int. J. Mol. Sci. 2025, 26(20), 10041; https://doi.org/10.3390/ijms262010041 - 15 Oct 2025
Cited by 1 | Viewed by 1525
Abstract
Minimally invasive surgery is known to lessen postoperative stress and complications compared with open procedures, yet its molecular effects on immunity and cancer-related mechanisms remain unclear. This study examined immune and inflammatory responses after robot-assisted (RS) versus open (OS) colorectal cancer surgery. Sixty-one [...] Read more.
Minimally invasive surgery is known to lessen postoperative stress and complications compared with open procedures, yet its molecular effects on immunity and cancer-related mechanisms remain unclear. This study examined immune and inflammatory responses after robot-assisted (RS) versus open (OS) colorectal cancer surgery. Sixty-one patients (RS = 30; OS = 31) were enrolled. Blood samples were collected before surgery and at 8, 24, and 72 h post-incision. Cytokines, growth factors, and prostanoids were measured using multiplex immunoassays and mass spectrometry to assess systemic immune and inflammatory changes. Surgery type markedly influenced perioperative immune profiles. RS induced stronger activation of Th1-associated cytokines, including IFNγ and IP-10, suggesting enhanced cellular immune responsiveness. In contrast, Th2 cytokines and other immunosuppressive mediators—such as IL-4, IL-10, and G-CSF—showed smaller or transient increases after RS, whereas OS triggered broader and more sustained elevations. Angiogenic factors (VEGF-A, PDGF-BB, FGF2) rose significantly after OS but remained comparatively lower and returned to baseline faster after RS, indicating a weaker proangiogenic response. Similarly, postoperative surges in prostaglandins linked to inflammation and tumor progression (PGE2, PGF2α) were blunted and resolved earlier following RS. Overall, the robotic approach was associated with reduced inflammatory and immunosuppressive activity, faster recovery of immune balance, and diminished biochemical signals favoring angiogenesis and potential tumor regrowth, suggesting a potential protective effect against pathogens and cancer-promoting mechanisms after colorectal tumor resection. Full article
(This article belongs to the Special Issue Colorectal Cancers: New Approach to Their Pathology, Diagnosis and Therapy)
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Review

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21 pages, 1548 KB  
Review
From CMS to iCMS/IMF: Developing Roadmap to Precision Therapy in Colorectal Cancer
by Sungwon Jung
Int. J. Mol. Sci. 2025, 26(22), 11086; https://doi.org/10.3390/ijms262211086 - 16 Nov 2025
Cited by 1 | Viewed by 1515
Abstract
Colorectal cancer (CRC) classification has progressed from consensus molecular subtypes (CMS) to epithelial–intrinsic consensus molecular subtypes (iCMS) and the layered intrinsic subtype-MSI-fibrosis (IMF) system that combines intrinsic state, MSI status, and fibrosis. This article reviews biological underpinnings of iCMS/IMF, their relationships to tumor-microenvironment [...] Read more.
Colorectal cancer (CRC) classification has progressed from consensus molecular subtypes (CMS) to epithelial–intrinsic consensus molecular subtypes (iCMS) and the layered intrinsic subtype-MSI-fibrosis (IMF) system that combines intrinsic state, MSI status, and fibrosis. This article reviews biological underpinnings of iCMS/IMF, their relationships to tumor-microenvironment crosstalk, and how single-cell and spatial transcriptomics refine therapeutic stratification by resolving tumor microenvironment heterogeneity and its impact on fibrosis. Prognostic and therapeutic implications are covered, including PD-1 blockade in MSI-high (MSI-H), MAPK-directed therapy in BRAF-mutant disease, and EGFR targeting in selected RAS wild-type (WT) left-sided tumors, and we suggest decision points specifically informed by the activity of the fibrosis axis. A step-by-step procedure is presented for the analysis of bulk and single-cell RNA and formalin-fixed, paraffin-embedded (FFPE) resources, along with open-source tools and reporting standards to make iCMS/IMF calling reproducible in clinics and trials. Future outlooks are outlined with near-term biomarker–drug hypotheses for microsatellite-stable (MSS)-iCMS3 and high fibrosis tumors and key gaps to close for clinical translation. This review outlines a roadmap for precision medicine in colorectal cancer by leveraging the iCMS/IMF framework to integrate pathology and digital pathology, molecular diagnostics, and therapy mapping with FAP-targeted imaging and therapy. Full article
(This article belongs to the Special Issue Colorectal Cancers: New Approach to Their Pathology, Diagnosis and Therapy)
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