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Cells
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Molecular Mechanisms of Liver Metastases
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Molecular Mechanisms of Liver Metastases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 19844

Special Issue Editors

Dr. Doris Wagner

E-Mail Website
Guest Editor
Department of Surgery, Medical University of Graz, 8036 Graz, Austria
Interests: liver surgery; liver; hepatobiliary surgery; pancreatic surgery; hepatopancreatobilliary surgery; surgical oncology; liver transplantation; liver cirrhosis; biliary tract diseases
Dr. Georgios Antonios Margonis

E-Mail Website
Guest Editor
1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
2. Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, 12203 Berlin, Germany
Interests: surgical oncology; hepatobiliary tumors; colorectal liver metastases; tumor biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

During the last few decades, several key factors that affect the prognosis of patients with colorectal liver metastasis (CRLM) have been defined. There have been exciting developments in identifying the genomic alterations in tumor cells, which allow us to better understand both the molecular mechanisms that mediate their aggressiveness as well as the crosstalk between tumor cells and the host microenvironment. These promising and innovative tools can potentially aid in the detection of disease progression and treatment of CRLM.

This Special Issue comprises articles that link metastasis mechanisms with clinical disease characteristics and patient outcomes. Publications on these mediators linking molecular mechanisms and clinical disease progression are of particular interest. For example, genomic alterations may be related to the occurrence of  micrometastases or distinct metastases growth patterns that lead to disease recurrence after surgery. The use of molecular markers, including the evolving field of liquid biopsies to detect ctDAN or for molecular diagnostics which allows a dynamic assessment of the interplay among genomic alterations, systemic therapies, and oncological outcomes to guide precision medicine (e.g., patient selection for adjuvant cytotoxic chemotherapy and biological therapies) and surgery opens opportunities for individually tailored approaches. Other topics of particular interest include the complex mechanisms of the natural progression of CRLM, including therapeutic strategies.

Dr. Doris Wagner
Dr. Georgios Antonios Margonis
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. Cells 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 2700 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

  • colorectal liver metastases (CRLM)
  • somatic mutations
  • tumor biology
  • gene alterations
  • RAS mutations

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Published Papers (5 papers)

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Editorial

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3 pages, 208 KiB  
Editorial
Gene Alterations, Mediators, and Artificial Intelligence in Colorectal Liver Metastases
by Doris Wagner and Georgios Antonios Margonis
Cells 2022, 11(14), 2205; https://doi.org/10.3390/cells11142205 - 15 Jul 2022
Viewed by 1514
Abstract
In this Special Issue of Cells, we seek articles that focus on the study of tumor biology in order to guide the scalpel [...] Full article
(This article belongs to the Special Issue Molecular Mechanisms of Liver Metastases)

Review

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14 pages, 1495 KiB  
Review
Somatic Mutations in Surgically Treated Colorectal Liver Metastases: An Overview
by Jane Wang, Julia Botvinov, Aarshvi Jahnvi Bhatt, Katharina Beyer, Martin E. Kreis, Mohamed Adam, Adnan Alseidi and Georgios Antonios Margonis
Cells 2024, 13(8), 679; https://doi.org/10.3390/cells13080679 - 14 Apr 2024
Cited by 1 | Viewed by 1923
Abstract
Colorectal cancer is the second most common cause of cancer death in the United States, and up to half of patients develop colorectal liver metastases (CRLMs). Notably, somatic genetic mutations, such as mutations in RAS, BRAF, mismatch repair (MMR) genes, TP53 [...] Read more.
Colorectal cancer is the second most common cause of cancer death in the United States, and up to half of patients develop colorectal liver metastases (CRLMs). Notably, somatic genetic mutations, such as mutations in RAS, BRAF, mismatch repair (MMR) genes, TP53, and SMAD4, have been shown to play a prognostic role in patients with CRLM. This review summarizes and appraises the current literature regarding the most relevant somatic mutations in surgically treated CRLM by not only reviewing representative studies, but also providing recommendations for areas of future research. In addition, advancements in genetic testing and an increasing emphasis on precision medicine have led to a more nuanced understanding of these mutations; thus, more granular data for each mutation are reviewed when available. Importantly, such knowledge can pave the way for precision medicine with the ultimate goal of improving patient outcomes. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Liver Metastases)
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16 pages, 1089 KiB  
Review
Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer
by Patrick W. Underwood, Samantha M. Ruff and Timothy M. Pawlik
Cells 2024, 13(3), 245; https://doi.org/10.3390/cells13030245 - 28 Jan 2024
Cited by 26 | Viewed by 8779
Abstract
Metastatic colorectal cancer remains a deadly malignancy and is the third leading cause of cancer-related death. The mainstay of treatment for metastatic colorectal cancer is chemotherapy, but unfortunately, even with recent progress, overall survival is still poor. Colorectal cancer is a heterogeneous disease, [...] Read more.
Metastatic colorectal cancer remains a deadly malignancy and is the third leading cause of cancer-related death. The mainstay of treatment for metastatic colorectal cancer is chemotherapy, but unfortunately, even with recent progress, overall survival is still poor. Colorectal cancer is a heterogeneous disease, and the underlying genetic differences among tumors can define the behavior and prognosis of the disease. Given the limitations of cytotoxic chemotherapy, research has focused on developing targeted therapy based on molecular subtyping. Since the early 2000s, multiple targeted therapies have demonstrated efficacy in treating metastatic colorectal cancer and have received FDA approval. The epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and DNA mismatch repair pathways have demonstrated promising results for targeted therapies. As new gene mutations and proteins involved in the oncogenesis of metastatic colorectal cancer are identified, new targets will continue to emerge. We herein provide a summary of the updated literature regarding targeted therapies for patients with mCRC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Liver Metastases)
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13 pages, 1356 KiB  
Review
Molecular Mechanisms of Colorectal Liver Metastases
by Diamantis I. Tsilimigras, Ioannis Ntanasis-Stathopoulos and Timothy M. Pawlik
Cells 2023, 12(12), 1657; https://doi.org/10.3390/cells12121657 - 18 Jun 2023
Cited by 12 | Viewed by 3893
Abstract
The liver is the most frequently target for metastasis among patients with colorectal cancer mainly because of the portal vein circulation that directly connects the colon and rectum with the liver. The liver tumor microenvironment consists of different cell types each with unique [...] Read more.
The liver is the most frequently target for metastasis among patients with colorectal cancer mainly because of the portal vein circulation that directly connects the colon and rectum with the liver. The liver tumor microenvironment consists of different cell types each with unique characteristics and functions that modulate the antigen recognition and immune system activation. Primary tumors from other sites “prime” the liver prior to the seeding of cancer cells, creating a pre-metastatic niche. Following invasion into the liver, four different phases are key to the development of liver metastases: a microvascular phase in which cancer cells infiltrate and become trapped in sinusoidal vessels; an extravascular, pre-angiogenic phase; an angiogenic phase that supplies oxygen and nutrients to cancer cells; and a growth phase in which metastatic cells multiply and enlarge to form detectable tumors. Exosomes carry proteins, lipids, as well as genetic information that can create a pre-metastatic niche in distant sites, including the liver. The complexity of angiogenic mechanisms and the exploitation of the vasculature in situ by cancer cells have limited the efficacy of currently available anti-angiogenic therapies. Delineating the molecular mechanisms implicated in colorectal liver metastases is crucial to understand and predict tumor progression; the development of distant metastases; and resistance to chemotherapy, immunotherapy, and targeted treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Liver Metastases)
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Other

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16 pages, 1520 KiB  
Systematic Review
Circulating Tumour DNA as Biomarker for Colorectal Liver Metastases: A Systematic Review and Meta-Analysis
by Lissa Wullaert, Jan M. van Rees, John W. M. Martens, Henk M. W. Verheul, Dirk J. Grünhagen, Saskia M. Wilting and Cornelis Verhoef
Cells 2023, 12(21), 2520; https://doi.org/10.3390/cells12212520 - 25 Oct 2023
Cited by 12 | Viewed by 2787
Abstract
Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver [...] Read more.
Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27–4.28, p < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53–10.04, p < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13–19.17, p < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Liver Metastases)
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