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Recent Advances in Basic and Clinical Colorectal Cancer Research

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 15 November 2024 | Viewed by 12387

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Special Issue Editors

Dr. Seiichi Shinji

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Guest Editor

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
Interests: gastroenterology; colorectal surgery; experimental pathology

Dr. Tomio Arai

E-Mail Website
Guest Editor

Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan
Interests: pathology; elderly cancer; colorectal cancer; gastric cancer; esophageal cancer

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the third most common cancer, and surgery remains the first-line management for patients with CRC. Despite advances in surgical techniques, chemotherapy, and radiotherapy, CRC remains the second leading cause of cancer-related death. There have been various advances in CRC management, including its diagnosis, endoscopic treatment, robotic surgery, targeted therapy, and precision medicine using artificial intelligence technology. This Special Issue provides and shares knowledge on the recent advances in basic and clinical CRC research.

This Special Issue welcomes original papers, review articles, and systematic reviews addressing in vitro and in vivo models for basic cancer research, as well as pre-clinical and clinical studies focusing on developing innovative diagnoses and treatments of CRC. We welcome a wide range of applications on any topic, including epidemiology, biomarker, microenvironment, morphofunctional diversity of colorectal cancer in 3D culture, early diagnosis, anti-cancer drug resistance, and genetic diagnosis.

We look forward to receiving your contributions.

Dr. Seiichi Shinji
Dr. Tomio Arai
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

anti-cancer therapies
animal models
in vitro assays
clinical trials
clinical oncology
translational medicine
metastasis
immune escape
mutation
targeted therapy

Published Papers (7 papers)

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Research

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17 pages, 6009 KiB

Open AccessArticle

Clinical Effectiveness of Fluorescence Lymph Node Mapping Using ICG for Laparoscopic Right Hemicolectomy: A Prospective Case–Control Study

by Gyung Mo Son, Mi Sook Yun, In Young Lee, Sun Bin Im, Kyung Hee Kim, Su Bum Park, Tae Un Kim, Dong-Hoon Shin, Armaan M. Nazir and Gi Won Ha

Cancers 2023, 15(20), 4927; https://doi.org/10.3390/cancers15204927 - 10 Oct 2023

Cited by 1 | Viewed by 980

Abstract

Background: The distinction between D3 lymph nodes and actual lymphatic pathways in primary tumors can be difficult during surgery, making it challenging to confirm the completeness of D3 lymph node dissection. Fluorescence lymph node mapping (FLNM) is a promising method for lymph node visualization. Purpose: This study aimed to assess whether FLNM enhances the effectiveness of D3 lymph node dissection in patients with right-sided colon cancer. Methods: Endoscopic submucosal indocyanine green injection were performed on the distal margin of the colon cancer. In an FLNM group, the lymphatic drainage pathway and distribution of D3 lymph nodes were explored. Pathological evaluations were conducted for the fluorescent D3 and non-fluorescent D3 lymph nodes. Results: The FLNM group showed a significantly higher number of harvested lymph nodes in the D3 area. In stage III patients, the proportion of D3 lymph node metastasis was significantly higher in the FLNM group. The harvested D3 lymph node count showed a proportional correlation with a metastatic lymph node count of up to 15. Conclusion: FLNM could be considered a promising new strategy to potentially increase harvested D3 lymph node counts in colon cancer surgery. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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16 pages, 6896 KiB

Open AccessArticle

World’s First Long-Term Colorectal Cancer Model by 3D Bioprinting as a Mechanism for Screening Oncolytic Viruses

by Colin McGuckin, Nico Forraz, Clément Milet, Mathieu Lacroix, Yordan Sbirkov, Victoria Sarafian, Caroline Ebel, Anita Spindler, Véronique Koerper, Jean-Marc Balloul, Eric Quéméneur and Cécile Zaupa

Cancers 2023, 15(19), 4724; https://doi.org/10.3390/cancers15194724 - 26 Sep 2023

Cited by 3 | Viewed by 2081

Abstract

Long-term modelization of cancer as it changes in the human body is a difficult goal, particularly when designing and testing new therapeutic strategies. This becomes even more difficult with metastasis modeling to show chemotherapeutic molecule delivery directly to tumoral cells. Advanced therapeutics, including oncolytic viruses, antibody-based and cell-based therapies are increasing. The question is, are screening tests also evolving? Next-generation therapeutics need equally advanced screening tests, which whilst difficult to achieve, are the goal of our work here, creating models of micro- and macrotumors using 3D bioprinting. We developed advanced colorectal cancer tumor processing techniques to provide options for cellular expansion, microtumor printing, and long-term models, which allow for the evaluation of the kinetics of penetration testing, therapeutic success, targeted therapies, and personalized medicine. We describe how we tested tumors from a primary colorectal patient and, applying 3D bioprinting, matured long-term models for oncolytic metastatic screening. Three-dimensional microtumors were kept alive for the longest time ever recorded in vitro, allowing longitudinal studies, screening of oncolytic viruses and realistic modelization of colorectal cancer. These 3D bioprinted models were maintained for around 6 months and were able to demonstrate the effective delivery of a product to the tumoral environment and represent a step forward in therapeutic screening. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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10 pages, 442 KiB

Open AccessArticle

Textbook Oncological Outcomes for Robotic Colorectal Cancer Resections: An Observational Study of Five Robotic Colorectal Units

by José Moreira Azevedo, Sofoklis Panteleimonitis, Danilo Mišković, Ignacio Herrando, Mahmood Al-Dhaheri, Mukhtar Ahmad, Tahseen Qureshi, Laura Melina Fernandez, Mick Harper and Amjad Parvaiz

Cancers 2023, 15(15), 3760; https://doi.org/10.3390/cancers15153760 - 25 Jul 2023

Cited by 1 | Viewed by 905

Abstract

Background: The quality of care of patients receiving colorectal resections has conventionally relied on individual metrics. When discussing with patients what these outcomes mean, they often find them confusing or overwhelming. Textbook oncological outcome (TOO) is a composite measure that summarises all the ‘desirable’ or ‘ideal’ postoperative clinical and oncological outcomes from both a patient’s and doctor’s point of view. This study aims to evaluate the incidence of TOO in patients receiving robotic colorectal cancer surgery in five robotic colorectal units and understand the risk factors associated with failure to achieve a TOO in these patients. Methods: We present a retrospective, multicentric study with data from a prospectively collected database. All consecutive patients receiving robotic colorectal cancer resections from five centres between 2013 and 2022 were included. Patient characteristics and short-term clinical and oncological data were collected. A TOO was achieved when all components were realized—no conversion to open, no complication with a Clavien–Dindo (CD) ≥ 3, length of hospital stay ≤ 14, no 30-day readmission, no 30-day mortality, and R0 resection. The main outcome measure was a composite measure of “ideal” practice called textbook oncological outcomes. Results: A total of 501 patients submitted to robotic colorectal cancer resection were included. Of the 501 patients included, 388 (77.4%) achieved a TOO. Four patients were converted to open (0.8%); 55 (11%) had LOS > 14 days; 46 (9.2%) had a CD ≥ 3 complication; 30-day readmission rate was 6% (30); 30-day mortality was 0.2% (1); and 480 (95.8%) had an R0 resection. Abdominoperineal resection was a risk factor for not achieving a TOO. Conclusions: Robotic colorectal cancer surgery in robotic centres achieves a high TOO rate. Abdominoperineal resection is a risk factor for failure to achieve a TOO. This measure may be used in future audits and to inform patients clearly on success of treatment. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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19 pages, 3306 KiB

Open AccessArticle

Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy

by Gabriela Sampaio-Ribeiro, Ana Ruivo, Ana Silva, Ana Lúcia Santos, Rui Caetano Oliveira, João Gama, Maria Augusta Cipriano, José Guilherme Tralhão and Artur Paiva

Cancers 2023, 15(12), 3222; https://doi.org/10.3390/cancers15123222 - 16 Jun 2023

Cited by 2 | Viewed by 1139

Abstract

Colorectal cancer (CRC) is the third most prevalent type of cancer, and liver metastasis is the most common site of metastatic development. In the tumor microenvironment (TME), various innate immune cells are known to influence cancer progression and metastasis occurrence. CD274 (PD-L1) and CD206 (MRC1) are proteins that have been associated with poor prognosis and disease progression. We conducted a study on tumoral and non-tumoral biopsies from 47 patients with CRC liver metastasis, using flow cytometry to phenotypically characterize innate immune cells. Our findings showed an increase in the expression of CD274 on classical, intermediate, and non-classical monocytes when comparing tumor with non-tumor samples. Furthermore, tumor samples with a desmoplastic growth pattern exhibited a significantly decreased percentage of CD274- and CD206-positive cells in all monocyte populations compared to non-desmoplastic samples. We found a correlation between a lower expression of CD206 or CD274 on classical, intermediate, and non-classical monocytes and increased disease-free survival, which points to a better prognosis for these patients. In conclusion, our study has identified potential new targets and biomarkers that could be incorporated into a personalized medicine approach to enhance the outcome for colorectal cancer patients. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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Graphical abstract

18 pages, 4444 KiB

Open AccessArticle

The Combination of ATM and Chk1 Inhibitors Induces Synthetic Lethality in Colorectal Cancer Cells

by Yuri Tozaki, Hiromasa Aoki, Rina Kato, Kohki Toriuchi, Saki Arame, Yasumichi Inoue, Hidetoshi Hayashi, Eiji Kubota, Hiromi Kataoka and Mineyoshi Aoyama

Cancers 2023, 15(3), 735; https://doi.org/10.3390/cancers15030735 - 25 Jan 2023

Viewed by 2195

Abstract

Genetic abnormalities induce the DNA damage response (DDR), which enables DNA repair at cell cycle checkpoints. Although the DDR is thought to function in preventing the onset and progression of cancer, DDR-related proteins are also thought to contribute to tumorigenesis, tumor progression, and drug resistance by preventing irreparable genomic abnormalities from inducing cell death. In the present study, the combination of ataxia telangiectasia-mutated serine/threonine kinase (ATM) and checkpoint kinase 1 (Chk1) inhibition exhibited synergistic antitumor effects and induced synergistic lethality in colorectal cancer cells at a low dose. The ATM and Chk1 inhibitors synergistically promoted the activation of cyclin-dependent kinase 1 by decreasing the phosphorylation levels of T14 and Y15. Furthermore, the combined treatment increased the number of sub-G1-stage cells, phospho-histone H2A.X-positive cells, and TdT-mediated dUTP nick-end labeling-positive cells among colon cancer cells, suggesting that the therapy induces apoptosis. Finally, the combined treatment exhibited a robust antitumor activity in syngeneic tumor model mice. These findings should contribute to the development of new treatments for colorectal cancer that directly exploit the genomic instability of cancer cells. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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14 pages, 1545 KiB

Open AccessArticle

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer

by Gonzalo Hijos-Mallada, Nuria Saura, Alberto Lué, Raúl Velamazan, Rocío Nieto, Mercedes Navarro, Samantha Arechavaleta, Eduardo Chueca, Fernando Gomollon, Angel Lanas and Carlos Sostres

Cancers 2023, 15(3), 721; https://doi.org/10.3390/cancers15030721 - 24 Jan 2023

Cited by 1 | Viewed by 1739

Abstract

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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Review

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18 pages, 1020 KiB

Open AccessReview

Unraveling Resistance to Immunotherapy in MSI-High Colorectal Cancer

by Ronald Heregger, Florian Huemer, Markus Steiner, Alejandra Gonzalez-Martinez, Richard Greil and Lukas Weiss

Cancers 2023, 15(20), 5090; https://doi.org/10.3390/cancers15205090 - 21 Oct 2023

Viewed by 2493

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths. Incidences of early CRC cases are increasing annually in high-income countries, necessitating effective treatment strategies. Immune checkpoint inhibitors (ICIs) have shown significant clinical efficacy in various cancers, including CRC. However, their effectiveness in CRC is limited to patients with mismatch-repair-deficient (dMMR)/microsatellite instability high (MSI-H) disease, which accounts for about 15% of all localized CRC cases and only 3% to 5% of metastatic CRC cases. However, the varied response among patients, with some showing resistance or primary tumor progression, highlights the need for a deeper understanding of the underlying mechanisms. Elements involved in shaping the response to ICIs, such as tumor microenvironment, immune cells, genetic changes, and the influence of gut microbiota, are not fully understood thus far. This review aims to explore potential resistance or immune-evasion mechanisms to ICIs in dMMR/MSI-H CRC and the cell types involved, as well as possible pitfalls in the diagnosis of this particular subtype. Full article

(This article belongs to the Special Issue Recent Advances in Basic and Clinical Colorectal Cancer Research)

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