Metastatic Colorectal Cancer: From Laboratory to Clinical Studies

Topic Information

Dear Colleagues,

Colorectal cancer (CRC) ranks third in terms of incidence among both men and women, and it is also the third most common cause of cancer-related death in the USA. It has always been acknowledged as a diverse disease, whose clinical course varies depending on the prognosis and response to treatment of each patient. Researchers and doctors are switching from a “one size fits all” approach to treating the disease to the identification of novel biomarkers that can be targeted to specifically treat each patient. The widespread use of next-generation sequencing techniques and liquid biopsies has enhanced our understanding of the molecular landscape of metastatic CRC. However, most patients with metastatic CRC need to receive treatment using a multimodal strategy that incorporates surgery, radiation, and chemotherapy/immunotherapy. Determining the molecular and cellular mechanisms underlying the onset and progression of this incurable cancer as well as the specific biomarkers connected to it will help with cancer detection and will improve prognosis. The core of tailored therapy in the twenty-first century is the multidisciplinary approach to the care of metastatic CRC, which combines fundamental and translational research with bedside clinical research. This Topic focuses on preclinical and clinical studies on metastatic CRC. We invite experts in molecular pathology, hematology–oncology, hematopathology, stem cells, immunotherapy, surgery, and other areas of cancer research to submit high-quality original studies or reviews related to the issues in this research area.

Dr. Ioannis Ntanasis-Stathopoulos
Dr. Diamantis I. Tsilimigras
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Cancers cancers	4.5	8.0	2009	16.3 Days	CHF 2900	Submit
Current Oncology curroncol	2.8	3.3	1994	17.6 Days	CHF 2200	Submit
Gastrointestinal Disorders gastrointestdisord	0.9	1.5	2019	25.5 Days	CHF 1200	Submit
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900	Submit
Journal of Clinical Medicine jcm	3.0	5.7	2012	17.3 Days	CHF 2600	Submit

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Published Papers (8 papers)

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All Cancers Current Oncology Gastrointestinal Disorders IJMS JCM

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16 pages, 4720 KiB  

Open AccessArticle

Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer

by Tetsuo Ishizaki, Masahiro Sugimoto, Yu Kuboyama, Junichi Mazaki, Kenta Kasahara, Tomoya Tago, Ryutaro Udo, Kenichi Iwasaki, Yutaka Hayashi and Yuichi Nagakawa

J. Clin. Med. 2024, 13(17), 5202; https://doi.org/10.3390/jcm13175202 - 2 Sep 2024

Viewed by 676

Abstract

Background/Objectives: The objective of this study was to investigate the metabolomic profiles of patients with colorectal cancer (CRC) across various stages of the disease. Methods: The plasma samples were obtained from 255 subjects, including patients with CRC in stages I-IV, polyps, [...] Read more.

Background/Objectives: The objective of this study was to investigate the metabolomic profiles of patients with colorectal cancer (CRC) across various stages of the disease. Methods: The plasma samples were obtained from 255 subjects, including patients with CRC in stages I-IV, polyps, and controls. We employed capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography triple quadrupole mass spectrometry to analyze hydrophilic metabolites comprehensively. The data were randomly divided into two groups, and consistent differences observed in both groups were analyzed. Results: Acetylated polyamines, such as N¹-acetylspermine and N¹, N¹²-diacetylspermine, consistently showed elevated concentrations in stage IV compared to stages I-III. Non-acetylated polyamines, including spermine and spermidine, exhibited increasing trends from polyp to stage IV. Other metabolites, such as histidine and o-acetylcarnitine, showed decreasing trends across stages. While acetylated polyamines have been reported as CRC detection markers, our findings suggest that they also possess diagnostic potential for distinguishing stage IV from other stages. Conclusions: This study showed stage-specific changes in metabolic profiles, including polyamines, of colorectal cancer. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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22 pages, 4178 KiB  

Open AccessArticle

Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study

by Juan Pablo Cayún, Leslie Carol Cerpa, Alicia Colombo, Dante Daniel Cáceres, José Luis Leal, Felipe Reyes, Carolina Gutiérrez-Cáceres, Susan Calfunao, Nelson Miguel Varela and Luis Abel Quiñones

Curr. Oncol. 2024, 31(1), 274-295; https://doi.org/10.3390/curroncol31010018 - 3 Jan 2024

Cited by 1 | Viewed by 2068

Abstract

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence [...] Read more.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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10 pages, 2450 KiB  

Open AccessFeature PaperArticle

Exosomes Derived from Colon Cancer Cells Promote Tumor Progression and Affect the Tumor Microenvironment

by Minsung Kim, Il Tae Son, Gyoung Tae Noh, So-Youn Woo, Ryung-Ah Lee and Bo Young Oh

J. Clin. Med. 2023, 12(12), 3905; https://doi.org/10.3390/jcm12123905 - 7 Jun 2023

Cited by 6 | Viewed by 2447

Abstract

Cancer-cell-derived exosomes confer oncogenic properties in their tumor microenvironment and to other cells; however, the exact mechanism underlying this process is unclear. Here, we investigated the roles of cancer-cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines, HT-29, SW480, [...] Read more.

Cancer-cell-derived exosomes confer oncogenic properties in their tumor microenvironment and to other cells; however, the exact mechanism underlying this process is unclear. Here, we investigated the roles of cancer-cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines, HT-29, SW480, and LoVo, using an ExoQuick-TC kit, identified using Western blotting for exosome markers, and characterized using transmission electron microscopy and nanosight tracking analysis. The isolated exosomes were used to treat HT-29 to evaluate their effect on cancer progression, specifically cell viability and migration. Cancer-associated fibroblasts (CAFs) were obtained from patients with colorectal cancer to analyze the effect of the exosomes on the tumor microenvironment. RNA sequencing was performed to evaluate the effect of the exosomes on the mRNA component of CAFs. The results showed that exosome treatment significantly increased cancer cell proliferation, upregulated N-cadherin, and downregulated E-cadherin. Exosome-treated cells exhibited higher motility than control cells. Compared with control CAFs, exosome-treated CAFs showed more downregulated genes. The exosomes also altered the regulation of different genes involved in CAFs. In conclusion, colon cancer-cell-derived exosomes affect cancer cell proliferation and the epithelial–mesenchymal transition. They promote tumor progression and metastasis and affect the tumor microenvironment. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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24 pages, 869 KiB  

Open AccessSystematic Review

Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review

by Emmanouil Georgilis, Maria Gavriatopoulou, Diamantis I. Tsilimigras, Panagiotis Malandrakis, Theodosios Theodosopoulos and Ioannis Ntanasis-Stathopoulos

J. Clin. Med. 2023, 12(6), 2401; https://doi.org/10.3390/jcm12062401 - 20 Mar 2023

Cited by 4 | Viewed by 2662

Abstract

The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to [...] Read more.

The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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13 pages, 949 KiB  

Open AccessArticle

The Resection Rate of Synchronously Detected Liver and Lung Metastasis from Colorectal Cancer Is Low—A National Registry-Based Study

by Jennie Engstrand, Helena Taflin, Jenny Lundmark Rystedt, Oskar Hemmingsson, Jozef Urdzik, Per Sandström, Bergthor Björnsson and Kristina Hasselgren

Cancers 2023, 15(5), 1434; https://doi.org/10.3390/cancers15051434 - 23 Feb 2023

Cited by 1 | Viewed by 2183

Abstract

Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide [...] Read more.

Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide population-based study of all patients having liver and lung metastases diagnosed within 6 months of CRC between 2008 and 2016 in Sweden identified through the merging of data from the National Quality Registries on CRC, liver and thoracic surgery and the National Patient Registry. Among 60,734 patients diagnosed with CRC, 1923 (3.2%) had synchronous liver and lung metastases, of which 44 patients had complete metastasectomy. Surgery of liver and lung metastases yielded a 5-year OS of 74% (95% CI 57–85%) compared to 29% (95% CI 19–40%) if liver metastases were resected but not the lung metastases and 2.6% (95% CI 1.5–4%) if non-resected, p < 0.001. Complete resection rates ranged from 0.7% to 3.8% between the six healthcare regions of Sweden, p = 0.007. Synchronous liver and lung CRC metastases are rare, and a minority undergo the resection of both metastatic sites but with excellent survival. The reasons for differences in regional treatment approaches and the potential of increased resection rates should be studied further. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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13 pages, 2257 KiB  

Open AccessArticle

Comparative Study of Short-Term Efficacy and Safety of Radical Surgery with or without Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer with T4 Stage: A Propensity Score Matching Analysis

by Xikai Guo, Yao Lin, Chu Shen, Yuan Li, Xinyu Zeng, Jianbo Lv, Fan Xiang, Tuo Ruan, Chuanqing Wu and Kaixiong Tao

J. Clin. Med. 2023, 12(3), 1145; https://doi.org/10.3390/jcm12031145 - 1 Feb 2023

Viewed by 1872

Abstract

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in T4 colorectal cancer (CRC) remains controversial. The study aimed to explore the safety and efficacy of radical surgery (RS) with HIPEC in T4 CRC. Methods: Adverse events after HIPEC were estimated by Common Terminology Criteria for Adverse [...] Read more.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in T4 colorectal cancer (CRC) remains controversial. The study aimed to explore the safety and efficacy of radical surgery (RS) with HIPEC in T4 CRC. Methods: Adverse events after HIPEC were estimated by Common Terminology Criteria for Adverse Events version 5.0. The efficacy was evaluated using recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was used to reduce the effects of confounders between groups. Results: Of the 417 patients (263 men and 154 women), 165 patients were treated with RS + HIPEC and 252 patients with RS alone. There was no significant difference in the incidence of all adverse events after PSM. Overall RFS and OS were not significantly different at 24 months (p = 0.580 and p = 0.072, respectively). However, in patients with T4b stage CRC (92.1% vs. 77.3%, p = 0.048) and tumor size ≥ 5 cm (93.0% vs. 80.9%, p = 0.029), RFS in the two groups showed a significant difference at 24 months. Conclusions: In summary, the safety of HIPEC in T4 CRC was confirmed. Compared with RS, though RS + HIPEC did not benefit the overall cohort at 24 months, RS + HIPEC could benefit patients with T4b stage CRC and tumor size ≥ 5 cm in RFS. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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35 pages, 1465 KiB  

Open AccessReview

Current Landscape and Potential Challenges of Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Carcinoma

by María San-Román-Gil, Javier Torres-Jiménez, Javier Pozas, Jorge Esteban-Villarrubia, Víctor Albarrán-Fernández, Pablo Álvarez-Ballesteros, Jesús Chamorro-Pérez, Diana Rosero-Rodríguez, Inmaculada Orejana-Martín, Íñigo Martínez-Delfrade, Pablo Reguera-Puertas, Raquel Fuentes-Mateos and Reyes Ferreiro-Monteagudo

Cancers 2023, 15(3), 863; https://doi.org/10.3390/cancers15030863 - 30 Jan 2023

Cited by 7 | Viewed by 4254

Abstract

Colorectal cancer (CRC) is the third most frequent cancer and the second most common cause of cancer-related death in Europe. High microsatellite instability (MSI-H) due to a deficient DNA mismatch repair (dMMR) system can be found in 5% of metastatic CRC (mCRC) and [...] Read more.

Colorectal cancer (CRC) is the third most frequent cancer and the second most common cause of cancer-related death in Europe. High microsatellite instability (MSI-H) due to a deficient DNA mismatch repair (dMMR) system can be found in 5% of metastatic CRC (mCRC) and has been established as a biomarker of response to immunotherapy in these tumors. Therefore, immune checkpoint inhibitors (ICIs) in mCRC with these characteristics were evaluated with results showing remarkable response rates and durations of response. The majority of mCRC cases have high levels of DNA mismatch repair proteins (pMMR) with consequent microsatellite stability or low instability (MSS or MSI-low), associated with an inherent resistance to ICIs. This review aims to provide a comprehensive analysis of the possible approaches to overcome the mechanisms of resistance and evaluates potential biomarkers to establish the role of ICIs in pMMR/MSS/MSI-L (MSS) mCRC. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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14 pages, 2358 KiB  

Open AccessArticle

Comparative Study of Short-Term Efficacy and Safety of Mitomycin versus Lobaplatin for Hyperthermic Intraperitoneal Chemotherapy after Radical Surgery in Colorectal Cancer with High-Risk Factors for Peritoneal Carcinomatosis: A Propensity Score Matching Analysis

by Xikai Guo, Yao Lin, Chu Shen, Yuan Li, Fan Xiang, Tuo Ruan, Xinyu Zeng, Jianbo Lv, Kaixiong Tao and Chuanqing Wu

Curr. Oncol. 2023, 30(2), 1488-1501; https://doi.org/10.3390/curroncol30020114 - 21 Jan 2023

Cited by 1 | Viewed by 2113

Abstract

Background: The drug selection of radical surgery (RS), with hyperthermic intraperitoneal chemotherapy (HIPEC), in pT4 colorectal cancer (CRC) remains controversial. Methods: Adverse events after HIPEC were estimated by common terminology criteria for adverse events version 5.0. The efficacy was evaluated using overall survival [...] Read more.

Background: The drug selection of radical surgery (RS), with hyperthermic intraperitoneal chemotherapy (HIPEC), in pT4 colorectal cancer (CRC) remains controversial. Methods: Adverse events after HIPEC were estimated by common terminology criteria for adverse events version 5.0. The efficacy was evaluated using overall survival (OS) and recurrence-free rate (RFR). Propensity score matching (PSM) was used to reduce the influence of confounders between Mitomycin and Lobaplatin groups. Results: Of the 146 patients, from April 2020 to March 2021, 47 were managed with mitomycin and 99 with lobaplatin. There was no significant difference in the incidence of all adverse events between the two groups after PSM. OS and RFR were not significantly different between the two groups at 22 months (p = 0.410; p = 0.310). OS and RFR of the two groups also showed no significant difference for patients with T4a or T4b stage, tumor size < or ≥ 5 cm. Among patients with colon cancer, RFR at 22 months of the two groups was significantly different (100.0% vs. 63.2%, p = 0.028). Conclusions: In summary, the safety of mitomycin and lobaplatin for HIPEC was not different. Compared with lobaplatin, mitomycin for HIPEC after RS could benefit patients with colon cancer in RFR. Full article

(This article belongs to the Topic Metastatic Colorectal Cancer: From Laboratory to Clinical Studies)

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