Pattern and Dynamics of Distant Metastases in Metastatic Colorectal Cancer

Holch, Julian Walter; Demmer, Maximilian; Lamersdorf, Charlotte; Michl, Marlies; Schulz, Christoph; Einem, Jobst C. von; Modest, Dominik Paul; Heinemann, Volker

doi:10.1159/000454687

Cited by 64 publications

(45 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5a-d). This is important, as the liver is the most common site of metastases from colorectal cancer: in clinical practice, up to half of all patients with colorectal cancer will develop hepatic metastases, with a median survival of only 8 months and a 5-year survival of less than 5% [26][27][28][29][30] . Another quorum sensing peptide (i.e.…”

Section: In Vivo Pro-metastatic Properties Of Entf* In Micementioning

confidence: 99%

The Quorum Sensing Peptide EntF* Promotes Colorectal Cancer Metastasis in Mice: A New Factor in the Microbiome-Host Interaction

Debunne

Wynendaele

Janssens

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundColorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide analyses between healthy individuals and cancer patients suggest a role for the human intestinal microbiota. Nevertheless, which microbial molecules are involved in this communication is largely unknown, with current studies mainly focusing on short chain fatty acids and amino acid metabolites as potential mediators. However, quorum sensing peptides are not yet considered in this microbiome-host interaction: their in vivo presence nor any in vivo host-effect have been reported.ResultsFor the first time, we showed that a quorum sensing peptide metabolite, EntF* produced by intestinal microbiota (E. faecium), is present in the blood circulation of mice. Moreover, it significantly promotes colorectal cancer metastasis in vivo, with metastatic lesions found in both liver and lung tissues, using an orthotopic mice model evaluating bioluminescence as well as macroscopic and microscopic presence of metastatic tumour nodules. In vitro tests on E-cadherin expression levels thereby indicated that the first, second, sixth and tenth amino acid of EntF* were critical for the epithelial-mesenchymal transition (EMT) effect, responsible for tumour metastasis.ConclusionThis paper adds a new group of molecules, the quorum sensing peptides, as an additional causative factor explaining the microbiome-host interaction. The presence of a selected quorum sensing peptide (metabolite) in the mouse was proven for the first time and its in vivo effect on colorectal metastasis was demonstrated. We anticipate our in vivo results to be a starting point for broader microbiome-health investigations, not only limited to colorectal cancer metastasis, but also for developing novel bio-therapeutics in other disease areas, giving due attention to the QSP produced by the microbiome.

show abstract

Section: In Vivo Pro-metastatic Properties Of Entf* In Micementioning

confidence: 99%

The Quorum Sensing Peptide EntF* Promotes Colorectal Cancer Metastasis in Mice: A New Factor in the Microbiome-Host Interaction

Debunne

Wynendaele

Janssens

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…It also appears more frequently in males than females and, in both genders combined, displays the fourth highest mortality rate, after lung, breast, and prostate cancer [1]. Studies suggest that roughly 50% of CRC cases develop synchronous or metachronous distant metastases, typically in the liver or lung [3].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Damilakis

Mavroudis

Sfakianaki

et al. 2020

Cancers

View full text Add to dashboard Cite

Immunotherapy has considerably increased the number of anticancer agents in many tumor types including metastatic colorectal cancer (mCRC). Anti-PD-1 (programmed death 1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitors (ICI) have been shown to benefit the mCRC patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, ICI is not effective in mismatch repair proficient (pMMR) colorectal tumors, which constitute a large population of patients. Several clinical trials evaluating the efficacy of immunotherapy combined with chemotherapy, radiation therapy, or other agents are currently ongoing to extend the benefit of immunotherapy to pMMR mCRC cases. In dMMR patients, MSI testing through immunohistochemistry and/or polymerase chain reaction can be used to identify patients that will benefit from immunotherapy. Next-generation sequencing has the ability to detect MSI-H using a low amount of nucleic acids and its application in clinical practice is currently being explored. Preliminary data suggest that radiomics is capable of discriminating MSI from microsatellite stable mCRC and may play a role as an imaging biomarker in the future. Tumor mutational burden, neoantigen burden, tumor-infiltrating lymphocytes, immunoscore, and gastrointestinal microbiome are promising biomarkers that require further investigation and validation.

show abstract

“…Little is known about the dynamics of metastases during the course of CRC. According to Holch et al ., only 3.4% of patients with metastatic colon cancer have isolated distal lymph node metastases …”

mentioning

confidence: 99%

“…According to Holch et al, only 3.4% of patients with metastatic colon cancer have isolated distal lymph node metastases. 4 The anatomical localization of the primary tumour does not fully capture the occurrence of different metastatic patterns in metastatic CRC. Additional factors are likely to contribute to the site-specific appearance of metastases.…”

mentioning

confidence: 99%