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Medicina
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Therapeutic Landscapes in Colorectal Carcinoma: Part II
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Therapeutic Landscapes in Colorectal Carcinoma: Part II

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 25 June 2024 | Viewed by 3466

Special Issue Editors

Prof. Dr. Maria Rosaria De Miglio

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Guest Editor
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, Italy
Interests: cancer transcriptome; cancer genetics and epigenetics; cancer metabolism; colorectal carcinoma; “triple negative” breast cancer; clear cell renal carcinoma; precision medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Antonio M Scanu

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Guest Editor
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy
Interests: genetic and epigenetic aberrations in colorectal carcinoma; MAP infection in IBD and IBS in humans; ultrasonography in Crohn’s disease stadiation; microbiota manipulation in IBD
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the most frequent cancer and the third most common cause of cancer-related mortality worldwide. A high number of patients with CRC have metastases already at diagnosis, and metastatic CRC is mainly an incurable disease.

CRC is considered a heterogeneous multifactorial disease showing drastically different prognoses and responses to treatment, indicating the relevance to understanding specific pathways abnormalities to improve diagnosis, prognosis, and therapeutic strategies. The opportunity to identify specific biomarkers and to detect unambiguous molecular targets, associated with early signs of cancer, will be instrumental to developing new targeted therapies and reducing mortality for CRC. Although different critical genes and pathways have been related to the pathogenesis of CRC, for many of these genomic alterations, the prognostic and predictive roles are not known and do not influence treatment decisions in metastatic conditions. Recently, the identification of K-RAS and more recently of NRAS gene mutations is a widely accepted molecular test in the clinical treatment decisions for mCRC. BRAF V600E mutation has been approved as a prognostic biomarker for identifying a cohort of patients who will have a more aggressive clinical outcome. Moreover, a relationship between MSI-high and impressive response to immune checkpoint blockade with anti-PD1 therapy in mCRC patients has been established.

Consequently, a better understanding of the available data and a further investigation of the molecular mechanisms responsible for CRC pathogenesis is vital in order to improve CRC prevention, clinical outcome, and therapy.

We invite you and your colleagues to submit your articles reporting on this topic. Original research articles or reviews focusing on the biochemical and molecular aspects associated with the pathogenesis of the human CRC; identification of circulating/tissue biomarkers in early diagnosis and management of CRC patients; and translational to clinical research on the innovative approaches for individualized therapy are invited.

Prof. Dr. Maria Rosaria De Miglio
Prof. Dr. Antonio M Scanu
Guest Editors

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. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). 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

  • clinical, pathological, oncologic, and surgical features
  • landscapes in immunologic and tailored therapies
  • prognostic and therapeutic biomarkers
  • microbiota in pathogenesis
  • epigenetic and genetic aberrations related to resistance to anticancer therapy
  • role of staminal cells in biology and cancer therapy
  • new drug and pharmacological approaches in cancer therapy
  • news in pathology

Published Papers (3 papers)

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Research

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16 pages, 4752 KiB  
Article
Association of Microsatellite Instability and Gene Expression Profile in Colorectal Carcinoma and Potential Implications for Therapy
by Muhammad G. Kibriya, Farzana Jasmine, Yuliia Khamkevych, Maruf Raza, Mohammed Kamal, Marc Bissonnette and Habibul Ahsan
Medicina 2024, 60(3), 348; https://doi.org/10.3390/medicina60030348 - 20 Feb 2024
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Abstract
Background and Objective: In sporadic colorectal carcinomas (CRC), microsatellite instability (MSI) pathways play important roles. Previously, we showed differences in DNA methylation patterns in microsatellite stable (MSS) colorectal carcinomas and MSI-CRC. In the current study, we explore the similarities and differences in gene [...] Read more.
Background and Objective: In sporadic colorectal carcinomas (CRC), microsatellite instability (MSI) pathways play important roles. Previously, we showed differences in DNA methylation patterns in microsatellite stable (MSS) colorectal carcinomas and MSI-CRC. In the current study, we explore the similarities and differences in gene expression profiles in MSS and MSI at the gene level and at the pathway level to better understand CRC pathogenesis and/or the potential for therapeutic opportunities. Material and Methods: Seventy-one CRC patients (MSI = 18, MSS = 53) were studied. Paired tumor and adjacent normal tissues were used for genome-wide gene expression assays. Result: At the gene level, we compared the list of differentially expressed genes (fold change (FC) ≥ 3 and FDR < 0.05) in tumor tissues compared to corresponding normal tissue in CRC patients with MSI tumors (190 genes) and MSS tumors (129 genes). Of these, 107 genes overlapped. The list of genes that were differentially expressed in MSI tumors only showed enrichment predominantly in two broad categories of pathways—(a) Inflammation-related pathways including the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, chemokine signaling, nuclear factor kappa B (NFκB) signaling, and cytokine-cytokine interactions, and (b) metabolism-related pathways, including retinol metabolism, steroid hormone biosynthesis, drug metabolism, pentose and glucoronate interconversions, and ascorbate and aldarate metabolism. The genes in inflammation-related pathways were up-regulated whereas genes in metabolism-related pathways were down-regulated in MSI tumor tissue. Pathway-level analysis also revealed similar results confirming the gene enrichment findings. For example, the 150 genes involved in the IL-17 signaling pathway were on average up-regulated by 1.19 fold (CI 1.16–1.21) in MSI compared to 1.14 fold (CI 1.13–1.16) in MSS patients (interaction p = 0.0009). Conclusions: We document an association between MSI status and differential gene expression that broadens our understanding of CRC pathogenesis. Furthermore, targeting one or more of these dysregulated pathways could provide the basis for improved therapies for MSI and MSS CRC. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma: Part II)
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9 pages, 1215 KiB  
Article
Pattern of Residual Submucosal Involvement after Neoadjuvant Therapy for Rectal Cancer: A Rationale for the Utility of Endoscopic Submucosal Resection
by Haidy Elazzamy, Monika Bhatt, Paul Mazzara, Mohammed Barawi, Amer Zeni and Amr Aref
Medicina 2023, 59(10), 1807; https://doi.org/10.3390/medicina59101807 - 11 Oct 2023
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Abstract
Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We [...] Read more.
Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with ‘skip lesions’ in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma: Part II)
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Review

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12 pages, 628 KiB  
Review
Harnessing Minimal Residual Disease as a Predictor for Colorectal Cancer: Promising Horizons Amidst Challenges
by Xiaofen Wen, Donatella Coradduzza, Jiaxin Shen, Antonio Mario Scanu, Maria Rosaria Muroni, Matteo Massidda, Vincenzo Rallo, Ciriaco Carru, Andrea Angius and Maria Rosaria De Miglio
Medicina 2023, 59(10), 1886; https://doi.org/10.3390/medicina59101886 - 23 Oct 2023
Cited by 3 | Viewed by 1312
Abstract
Minimal Residual Disease (MRD) detection has emerged as an independent factor in clinical and pathological cancer assessment offering a highly effective method for predicting recurrence in colorectal cancer (CRC). The ongoing research initiatives such as the DYNAMIC and CIRCULATE-Japan studies, have revealed the [...] Read more.
Minimal Residual Disease (MRD) detection has emerged as an independent factor in clinical and pathological cancer assessment offering a highly effective method for predicting recurrence in colorectal cancer (CRC). The ongoing research initiatives such as the DYNAMIC and CIRCULATE-Japan studies, have revealed the potential of MRD detection based on circulating tumor DNA (ctDNA) to revolutionize management for CRC patients. MRD detection represents an opportunity for risk stratification, treatment guidance, and early relapse monitoring. Here we overviewed the evolving landscape of MRD technology and its promising applications through the most up-to-date research and reviews, underscoring the transformative potential of this approach. Our primary focus is to provide a point-to-point perspective and address key challenges relating to the adoption of ctDNA-based MRD detection in the clinical setting. By identifying critical areas of interest and hurdles surrounding clinical significance, detection criteria, and potential applications of basic research, this article offers insights into the advancements needed to evaluate the role of ctDNA in CRC MRD detection, contributing to favorable clinical options and improved outcomes in the management of CRC. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma: Part II)
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