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Fundamental and Translational Insights into Colorectal Cancer
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Fundamental and Translational Insights into Colorectal Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 984

Special Issue Editor

Dr. Giuseppe Broggi

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Anatomic Pathology, University of Catania, I-95123 Catania, Italy
Interests: histopathology; neuropathology; histological diagnosis; brain tumors; surgical pathology

Special Issue Information

Dear colleague,

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, driven by genetic, epigenetic, and environmental factors. Fundamental research has identified key molecular pathways involved in CRC, including mutations in APC, KRAS, and TP53, as well as the role of the Wnt/β-catenin signaling pathway. Emerging insights into the tumor microenvironment, immune response, and gut microbiota have further expanded our understanding of CRC progression.

Translational research is bridging the gap between these discoveries and clinical applications, leading to advancements in early detection, targeted therapies, and immunotherapy. Liquid biopsy and circulating tumor DNA analysis are improving non-invasive diagnostics. Novel treatments, such as immune checkpoint inhibitors and personalized medicine approaches, are showing promise in improving patient outcomes.

Despite these advancements, challenges remain, including drug resistance and tumor heterogeneity. The continued integration of fundamental and translational research is essential for developing innovative therapies and improving survival rates in patients with CRC.

Dr. Giuseppe Broggi
Guest Editor

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 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 (CRC)
  • molecular pathways
  • translational research
  • immune checkpoint inhibitors
  • drug resistance

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Published Papers (3 papers)

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Research

12 pages, 996 KB  
Article
Augmentation of the Benzyl Isothiocyanate-Induced Antiproliferation by NBDHEX in the HCT-116 Human Colorectal Cancer Cell Line
by Ruitong Sun, Aina Yano, Ayano Satoh, Shintaro Munemasa, Yoshiyuki Murata, Toshiyuki Nakamura and Yoshimasa Nakamura
Int. J. Mol. Sci. 2025, 26(17), 8145; https://doi.org/10.3390/ijms26178145 - 22 Aug 2025
Viewed by 120
Abstract
Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we [...] Read more.
Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC–glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC–GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses. Full article
(This article belongs to the Special Issue Fundamental and Translational Insights into Colorectal Cancer)
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17 pages, 5121 KB  
Article
Cholesterol-Conjugated Polyion Complex Nanoparticles for Combination Delivery of Hydrophobic Paclitaxel and Hydrophilic miR-34a for Colon Cancer Therapy
by Arjaree Jobdeedamrong, Hye Jin Yoo, Hosun Jung, Chiravoot Pechyen, Sitakan Natphopsuk, Peerapat Thongnuek, Seok Jeong, Junghan Lee and Su-Geun Yang
Int. J. Mol. Sci. 2025, 26(16), 7965; https://doi.org/10.3390/ijms26167965 - 18 Aug 2025
Viewed by 274
Abstract
In recent years, combination chemotherapy with therapeutic nucleic acids has emerged as a promising strategy to enhance the effectiveness of cancer therapy. However, developing an effective co-delivery system to simultaneously transport both chemotherapeutic drugs and nucleic acids remains challenging. Herein, we fabricated cholesterol-conjugated [...] Read more.
In recent years, combination chemotherapy with therapeutic nucleic acids has emerged as a promising strategy to enhance the effectiveness of cancer therapy. However, developing an effective co-delivery system to simultaneously transport both chemotherapeutic drugs and nucleic acids remains challenging. Herein, we fabricated cholesterol-conjugated polyion complex nanoparticles (PCNs) for combination delivery of hydrophobic paclitaxel (PTX) and hydrophilic miR-34a. Cholesterol was conjugated to polyethylenimine (PEI) and hyaluronic acid (HA), producing C–PEI and C–HA, respectively. PTX was initially encapsulated within the hydrophobic core formed by the self-assembly of C–HA and C–PEI, yielding polyion complex nanoparticles (PTX@C–HA/C–PEI PCNs). Subsequently, the negatively charged miR-34a was electrostatically complexed with the cationic C–PEI moieties to generate miR-34a/PTX@C–HA/C–PEI PCNs. These PCNs exhibited a nanoscale structure with a uniform size distribution and demonstrated low cytotoxicity in colon cancer cells. Fluorescence microscopy confirmed efficient cytosolic delivery of C–HA/C–PEI PCNs in colon carcinoma cells. Furthermore, combination delivery of PTX and miR-34a using C–HA/C–PEI PCNs exhibited significantly enhanced transfection efficiency and cellular uptake for human colon cancer cells. Notably, PTX/miR-34a@C–HA/C–PEI PCNs effectively downregulated critical oncogenic targets, including Notch1, Snail1, and BCL-2, resulting in reduced cancer cell migration and proliferation. These findings indicate that PTX/miR-34a@C–HA/C–PEI PCNs hold significant potential as an innovative combination delivery platform, offering improved therapeutic efficacy for colon cancer therapy. Full article
(This article belongs to the Special Issue Fundamental and Translational Insights into Colorectal Cancer)
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Graphical abstract

22 pages, 3029 KB  
Article
Epigenetic Remodeling of Regulatory Regions by Indicaxanthin Suggests a Shift in Cell Identity Programs in Colorectal Cancer Cells
by Maria Antonietta Ragusa, Carla Gentile, Aldo Nicosia, Salvatore Costa, Sara Volpes, Laura Greco, Flores Naselli and Fabio Caradonna
Int. J. Mol. Sci. 2025, 26(13), 6072; https://doi.org/10.3390/ijms26136072 - 24 Jun 2025
Cited by 1 | Viewed by 445
Abstract
Aberrant DNA methylation is a hallmark of colorectal cancer (CRC), contributing to tumor progression through the silencing of tumor suppressor genes and activation of oncogenes. Indicaxanthin (IND), a dietary betalain pigment from Opuntia ficus indica, has shown antiproliferative effects in CRC models, [...] Read more.
Aberrant DNA methylation is a hallmark of colorectal cancer (CRC), contributing to tumor progression through the silencing of tumor suppressor genes and activation of oncogenes. Indicaxanthin (IND), a dietary betalain pigment from Opuntia ficus indica, has shown antiproliferative effects in CRC models, yet its epigenetic impact remains unexplored. In this study, we investigated the effects of IND on the methylome of Caco-2 cells using Reduced Representation Bisulfite Sequencing (RRBS). IND induced a global hypermethylation profile, particularly at gene promoters and CpG islands. Among the differentially methylated genes, 60% were protein-coding, and 10% encoded transcription factors, including PAX5 and TFAP4, both hypermethylated at active enhancers. Functional enrichment analysis revealed pathways beyond canonical intestinal functions, suggesting altered cell identity and plasticity. Transcription factor targets (SOX10, NFKB1, AHR, ARNT) were significantly enriched among the affected genes, several of which are involved in transdifferentiation processes. Methylation changes also indicated potential reprogramming toward epithelial cell types from pulmonary or neuroectodermal origin. Moreover, IND induced selective hypomethylation of Alu elements on chromosome 21 and hypermethylation of rDNA loci, hinting at suppressed ribosomal biogenesis. Overall, these findings highlight the epigenetic remodeling potential of IND and its possible role in modulating cell fate and metabolism in CRC cells. Full article
(This article belongs to the Special Issue Fundamental and Translational Insights into Colorectal Cancer)
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