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Molecular Mechanisms and Therapies of Colorectal Cancer: 4th Edition
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Molecular Mechanisms and Therapies of Colorectal Cancer: 4th Edition

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: 31 May 2025 | Viewed by 3051

Special Issue Editor

Dr. Donatella Delle Cave

E-Mail Website
Guest Editor
Institute of Genetics and Biophysics "A. Buzzati Traverso" (IGB-ABT), CNR, Via Pietro Castellino 111, 80131 Naples, Italy
Interests: pancreatic cancer; cancer stem cells; tumor microenvironment; cancer metabolism; fibrosis; TGF-β signaling; target therapy; drug delivery systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality. Transforming growth factor beta (TGF-β) signaling has been associated with CRC growth and metastasis due to its involvement in proliferation, epithelial-to-mesenchymal transition (EMT), and angiogenesis. The TGF-β superfamily contains over forty members, including TGF-βs, Nodal, Activin, and bone morphogenetic proteins (BMPs). Three types of TGF-β receptors (TGFβR) have been identified: types 1, 2, and 3. After ligand binding, TGF-βR2 recruits and phosphorylates TGF-βR1 that in turn phosphorylates downstream SMAD (small mother against decapentaplegic) proteins. Phosphorylated SMAD4 translocates into the nucleus, where it activates the transcription of numerous target genes (including SERPINE1, LTBP2, CDKN1A, ARID3B, ATXN1, PTPRK, RAB6A, SMAD7, EHBP1, etc.), acting predominantly as a tumor-suppressor gene. Interestingly, alterations of SMAD4 are frequent in metastatic CRC and, together with TGF-βR2 genes mutations, have been reported as late events able to promote CRC progression. The study of TGF-β pathway in metastatic CRC is challenging because of the great genetic heterogeneity of CRC. However, the increasing availability of targeted and whole-exome DNA sequencing techniques makes it possible to identify genes’ mutations in complex, dynamic, and heterogeneous clinical contexts and to make correlations with clinical outcome.

This Special Issue was established to prompt researchers to perform studies on:

  • Involvement of the TGF-β pathway in metastatic CRC;
  • Emerging methods to identify and correlate specific TGF-β pathway genes’ mutations with metastatic behavior;
  • Novel approaches to target the TGF-β pathway in metastatic CRC;
  • Novel studies to depict TGF-β pathway evolution from primary to metastatic lesions.

Articles consisting exclusively of bioinformatics or computational analyses of public databases or pure clinical studies will not be accepted. Basic studies or translational studies including molecular characterizations of patients from real practice are welcome. Reviews will also be appreciated.

Dr. Donatella Delle Cave
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.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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

  • transforming growth factor beta (TGF-β) signaling
  • genetic alterations
  • molecular targeted therapy precision medicine

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Published Papers (3 papers)

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Research

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10 pages, 4621 KiB  
Article
Lymphangiogenesis in the Deepest Invasive Areas of Human Early-Stage Colorectal Cancer
by Masaharu Tanaka, Qian Zhou, Minako Ohnishi, Miho Kandori, Ami Itou, Yuki Kitadai, Hidehiko Takigawa, Shiro Oka, Akiko Kimoto, Fumio Shimamoto and Yasuhiko Kitadai
Int. J. Mol. Sci. 2025, 26(7), 2919; https://doi.org/10.3390/ijms26072919 - 24 Mar 2025
Viewed by 337
Abstract
Tumor-associated macrophages (TAMs) are known to induce epithelial–mesenchymal transition (EMT) and angiogenesis in areas with a high density of accumulation in the submucosal (SM) layer. However, lymphatic vessels, which are important routes for lymph node metastasis, have rarely been analyzed, and their relationship [...] Read more.
Tumor-associated macrophages (TAMs) are known to induce epithelial–mesenchymal transition (EMT) and angiogenesis in areas with a high density of accumulation in the submucosal (SM) layer. However, lymphatic vessels, which are important routes for lymph node metastasis, have rarely been analyzed, and their relationship to TAM accumulation is unknown. In this study, paraffin-embedded sections from 11 cases of human early-stage colorectal cancer (SM invasive carcinoma) were stained with CD34 antibody for vascular endothelium and podoplanin antibody for lymphatic endothelium at the deepest, central, and marginal sites of tumor invasion. Tumor blood vessels increased in the deepest invasive areas, and a positive correlation was observed between the number of TAMs and tumor blood vessels. Interestingly, lymphatic vessels with CD34-positive endothelial cells (CD34-positive lymphatic vessels) were observed within the tumor. The number of CD34-positive lymphatic vessels was significantly higher in the metastasis-positive group. These results suggest that abnormalities in the vascular and lymphatic systems are observed from the early stage of colorectal cancer development and that VEGF-A derived from TAMs is important for tumor angiogenesis. In addition, CD34-positive lymphatic vessels observed in the deepest areas of tumor invasion have not been reported in Japan, with initial reports indicating that they are neoplastic lymphatic vessels. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Colorectal Cancer: 4th Edition)
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15 pages, 7435 KiB  
Article
Fecal Microbiota Strongly Correlates with Tissue Microbiota Composition in Colorectal Cancer but Not in Non-Small Cell Lung Cancer
by Juan Vicente-Valor, Sofía Tesolato, Mateo Paz-Cabezas, Dulcenombre Gómez-Garre, Adriana Ortega-Hernández, Sofía de la Serna, Inmaculada Domínguez-Serrano, Jana Dziakova, Daniel Rivera, Jose-Ramón Jarabo, Ana-María Gómez-Martínez, Florentino Hernando, Antonio Torres and Pilar Iniesta
Int. J. Mol. Sci. 2025, 26(2), 717; https://doi.org/10.3390/ijms26020717 - 16 Jan 2025
Cited by 1 | Viewed by 923
Abstract
Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree [...] Read more.
Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree of correlation between the composition of the tissue microbiota and that of the feces of patients affected by CRC and NSCLC. Specifically, we investigated tumor and non-tumor tissues from 38 recruited patients with CRC and 19 with NSCLC. DNA from samples was submitted for 16S rDNA metagenomic sequencing, followed by data analysis through the QIIME2 pipeline and further statistical processing with STATA IC16. Tumor and non-tumor tissue selected genera were highly correlated in both CRC and NSCLC (100% and 81.25%). Following this, we established tissue–feces correlations, using selected genera from a LEfSe analysis previously published. In CRC, we found a strong correlation between the taxa detected in feces and those from colorectal tissues. However, our data do not demonstrate this correlation in NSCLC. In conclusion, our findings strongly reinforce the utility of fecal microbiota as a non-invasive biomarker for CRC diagnosis, while highlighting critical distinctions for NSCLC. Furthermore, our data demonstrate that the microbiota components of tumor and non-tumor tissues are similar, with only minor differences being detected. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Colorectal Cancer: 4th Edition)
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Review

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14 pages, 789 KiB  
Review
Understanding microRNA-Mediated Chemoresistance in Colorectal Cancer Treatment
by Guillermo Valenzuela, Héctor R. Contreras, Katherine Marcelain, Mauricio Burotto and Jaime González-Montero
Int. J. Mol. Sci. 2025, 26(3), 1168; https://doi.org/10.3390/ijms26031168 - 29 Jan 2025
Viewed by 1220
Abstract
Colorectal cancer (CRC) remains the second most lethal cancer worldwide, with incidence rates expected to rise substantially by 2040. Although biomarker-driven therapies have improved treatment, responses to standard chemotherapeutics, such as 5-fluorouracil (5-FU), oxaliplatin, and irinotecan, vary considerably. This clinical heterogeneity emphasizes the [...] Read more.
Colorectal cancer (CRC) remains the second most lethal cancer worldwide, with incidence rates expected to rise substantially by 2040. Although biomarker-driven therapies have improved treatment, responses to standard chemotherapeutics, such as 5-fluorouracil (5-FU), oxaliplatin, and irinotecan, vary considerably. This clinical heterogeneity emphasizes the urgent need for novel biomarkers that can guide therapeutic decisions and overcome chemoresistance. microRNAs (miRNAs) have emerged as key post-transcriptional regulators that critically influence chemotherapy responses. miRNAs orchestrate post-transcriptional gene regulation and modulate diverse pathways linked to chemoresistance. They influence drug transport by regulating ABC transporters and affect metabolic enzymes like thymidylate synthase (TYMS). These activities shape responses to standard CRC chemotherapy agents. Furthermore, miRNAs can regulate the epithelial–mesenchymal transition (EMT). The miR-200 family (e.g., miR-200c and miR-141) can reverse EMT phenotypes, restoring chemosensitivity. Additionally, miRNAs like miR-19a and miR-625-3p show predictive value for chemotherapy outcomes. Despite these promising findings, the clinical translation of miRNA-based biomarkers faces challenges, including methodological inconsistencies and the dynamic nature of miRNA expression, influenced by the tumor microenvironment. This review highlights the critical role of miRNAs in elucidating chemoresistance mechanisms and their promise as biomarkers and therapeutic targets in CRC, paving the way for a new era of precision oncology. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Colorectal Cancer: 4th Edition)
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