2nd Edition: Colorectal Cancers

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

Deadline for manuscript submissions: closed (20 October 2023) | Viewed by 8533

Special Issue Editors


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Guest Editor
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canad
Interests: cancer; stem cells; epigenetics; digestive systems; pharmacology
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Guest Editor
Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada
Interests: colorectal cancer; integrins and cell-extracellular matrix interactions; oncogenes; transcription; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous Special Issue "Colorectal Cancers": https://www.mdpi.com/journal/cancers/special_issues/Colorectal_Cancers

Colorectal cancer is one of the most common cancers worldwide, and it is predicted that the number of cases will continue to rise over the next 20 years. Despite the recent progress in screening techniques and the improvements in treatments, bowel cancer remains a significant cause of cancer mortality. A better comprehension of the cellular and molecular bases underlying colorectal neoplasm initiation and progression, from adenoma to metastasis, is crucial to establishing non-invasive and efficient detection tests for the identification of lesions at early stages, as well as for refining current therapeutic approaches and developing new ones useful in advanced stages of the disease.

In this Special Issue, we aim to cover all aspects of colorectal cancer research. To this end, we welcome articles on basic, preclinical, and clinical research on colorectal cancer.

Dr. Yannick D. Benoit
Prof. Dr. Jean-Francois Beaulieu
Guest Editors

Manuscript Submission Information

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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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • advances in early detection of colorectal lesions
  • biomarkers for assessing colorectal cancer
  • colorectal cancer stem cells
  • colorectal carcinogenesis and metastasis
  • colorectal tumor microenvironment
  • drug delivery to colorectal cancer cells
  • epigenetics of colorectal cancer
  • genetics and genomics of colorectal cancer
  • imaging of colorectal lesions
  • inflammatory bowel diseases and colorectal carcinogenesis
  • microbiome and colorectal cancer
  • molecular targeted therapies for colorectal cancer
  • mouse models of colorectal cancer
  • precision medicine for colorectal cancer
  • signaling pathways in colorectal cancer cells

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Published Papers (4 papers)

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Research

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27 pages, 3371 KiB  
Article
Identification of Gut Microbiota Profile Associated with Colorectal Cancer in Saudi Population
by Areej A. Alhhazmi, Yahya A. Almutawif, Walaa A. Mumena, Shaima M. Alhazmi, Turki S. Abujamel, Ruba M. Alhusayni, Raghad Aloufi, Razan R. Al-Hejaili, Rahaf Alhujaily, Lama M. Alrehaili, Ruya A. Alsaedy, Rahaf H. Khoja, Wassal Ahmed, Mohamed F. Abdelmohsen and Waleed Mohammed-Saeid
Cancers 2023, 15(20), 5019; https://doi.org/10.3390/cancers15205019 - 17 Oct 2023
Cited by 1 | Viewed by 2649
Abstract
Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression. This study aims to analyze the gut microbiota composition and the enriched metabolic pathways in patients with late-stage CRC. In this [...] Read more.
Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression. This study aims to analyze the gut microbiota composition and the enriched metabolic pathways in patients with late-stage CRC. In this study, a cohort of 25 CRC patients diagnosed at late stage III and IV and 25 healthy participants were enrolled. The fecal bacterial composition was investigated using V3-V4 ribosomal RNA gene sequencing, followed by clustering and linear discriminant analysis (LDA) effect size (LEfSe) analyses. A cluster of ortholog genes’ (COG) functional annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify enrichment pathways between the two groups. The findings showed that the fecal microbiota between the two groups varied significantly in alpha and beta diversities. CRC patients’ fecal samples had significantly enriched populations of Streptococcus salivarius, S. parasanguins, S. anginosus, Lactobacillus mucosae, L. gasseri, Peptostreptococcus, Eubacterium, Aerococcus, Family XIII_AD3001 Group, Erysipelatoclostridium, Escherichia-Shigella, Klebsiella, Enterobacter, Alistipes, Ralstonia, and Pseudomonas (Q < 0.05). The enriched pathways identified in the CRC group were amino acid transport, signaling and metabolism, membrane biogenesis, DNA replication and mismatch repair system, and protease activity (Q < 0.05). These results suggested that the imbalance between intestinal bacteria and the elevated level of the predicated functions and pathways may contribute to the development of advanced CRC tumors. Further research is warranted to elucidate the exact role of the gut microbiome in CRC and its potential implications for use in diagnostic, prevention, and treatment strategies. Full article
(This article belongs to the Special Issue 2nd Edition: Colorectal Cancers)
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Review

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20 pages, 1163 KiB  
Review
Immunotherapy for Colorectal Cancer with High Microsatellite Instability: The Ongoing Search for Biomarkers
by Javier Ros, Iosune Baraibar, Nadia Saoudi, Marta Rodriguez, Francesc Salvà, Josep Tabernero and Elena Élez
Cancers 2023, 15(17), 4245; https://doi.org/10.3390/cancers15174245 - 24 Aug 2023
Cited by 8 | Viewed by 2693
Abstract
Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. [...] Read more.
Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. Following the impressive clinical activity of immune checkpoint inhibitors in the metastatic setting, associated with deep and long-lasting responses, the development of immune checkpoint inhibitors has expanded to early-stage disease. Several phase II trials have demonstrated a high rate of pathological complete responses, with some patients even spared from surgery. However, in both settings, not all patients respond and some responses are short, emphasizing the importance of the ongoing search for accurate biomarkers. While various biomarkers of response have been evaluated in the context of MSI CRC, including B2M and JAK1/2 mutations, TMB, WNT pathway mutations, and Lynch syndrome, with mixed results, liver metastases have been associated with a lack of activity in such strategies. To improve patient selection and treatment outcomes, further research is required to identify additional biomarkers and refine existing ones. This will allow for the development of personalized treatment approaches and the integration of novel therapeutic strategies for MSI CRC patients with liver metastases. Full article
(This article belongs to the Special Issue 2nd Edition: Colorectal Cancers)
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Other

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9 pages, 615 KiB  
Commentary
Colorectal Cancer Is Borrowing Blueprints from Intestinal Ontogenesis
by Jacob L. Billingsley, Veronika Yevdokimova, Kristina Ayoub and Yannick D. Benoit
Cancers 2023, 15(20), 4928; https://doi.org/10.3390/cancers15204928 - 11 Oct 2023
Cited by 1 | Viewed by 1296
Abstract
Colorectal tumors are heterogenous cellular systems harboring small populations of self-renewing and highly tumorigenic cancer stem cells (CSCs). Understanding the mechanisms fundamental to the emergence of CSCs and colorectal tumor initiation is crucial for developing effective therapeutic strategies. Two recent studies have highlighted [...] Read more.
Colorectal tumors are heterogenous cellular systems harboring small populations of self-renewing and highly tumorigenic cancer stem cells (CSCs). Understanding the mechanisms fundamental to the emergence of CSCs and colorectal tumor initiation is crucial for developing effective therapeutic strategies. Two recent studies have highlighted the importance of developmental gene expression programs as potential therapeutic targets to suppress pro-oncogenic stem cell populations in the colonic epithelium. Specifically, a subset of aberrant stem cells was identified in preneoplastic intestinal lesions sharing significant transcriptional similarities with fetal gut development. In such aberrant stem cells, Sox9 was shown as a cornerstone for altered cell plasticity, the maintenance of premalignant stemness, and subsequent colorectal tumor initiation. Independently, chemical genomics was used to identify FDA-approved drugs capable of suppressing neoplastic self-renewal based on the ontogenetic root of a target tumor and transcriptional programs embedded in pluripotency. Here, we discuss the joint conclusions from these two approaches, underscoring the importance of developmental networks in CSCs as a novel paradigm for identifying therapeutics targeting colorectal cancer stemness. Full article
(This article belongs to the Special Issue 2nd Edition: Colorectal Cancers)
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6 pages, 693 KiB  
Commentary
Where to Draw the LINE—Are Retrotransposable Elements Here to Stay?
by Christopher J. Bergin, Amanda Mendes da Silva and Yannick D. Benoit
Cancers 2023, 15(16), 4119; https://doi.org/10.3390/cancers15164119 - 16 Aug 2023
Viewed by 1224
Abstract
The frequency of somatic retrotranspositions of Long Interspersed Nuclear Elements 1 (LINE1) over a lifetime in healthy colonic epithelium and colorectal tumors has recently been reported. Indicative of a cell type-specific effect, LINE1 sequences in colonic epithelium showed lower levels of DNA methylation [...] Read more.
The frequency of somatic retrotranspositions of Long Interspersed Nuclear Elements 1 (LINE1) over a lifetime in healthy colonic epithelium and colorectal tumors has recently been reported. Indicative of a cell type-specific effect, LINE1 sequences in colonic epithelium showed lower levels of DNA methylation compared to other cell types examined in the study. Consistent with a role for DNA methylation in transposon silencing, the decreases in DNA methylation observed at LINE1 elements in colonic epithelium were accompanied by increases in LINE1 mRNA levels. In human primary colorectal tumors, LINE1 retrotransposition frequency was tenfold higher than in normal colonic tissues, with insertions potentially altering genomic stability and cellular functions. Here, we discuss the discoveries made by Nam and colleagues, emphasizing the intestinal-specific methylation signature regulating the LINE1 lifecycle and how this new information could shape future drug discovery endeavors against colorectal cancer. Full article
(This article belongs to the Special Issue 2nd Edition: Colorectal Cancers)
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