Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial
Background: Colorectal cancer (CRC) is one of the most prevalent tumour types and a leading cause of cancer-related mortality worldwide. Surgery represents the primary therapeutic option, while advanced cases are typically managed with established chemotherapy protocols, which exhibit variable respo...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | ESMO Gastrointestinal Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S294981982500038X |
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| author | S. De Dosso D. Christoforidis E. Merlo A. Vannelli S. Popeskou P. Gaffuri G. Lollo L. Ambrosiani F. Radaelli M. Frattini M. Marengo K. Galetti G. Iezzi |
| author_facet | S. De Dosso D. Christoforidis E. Merlo A. Vannelli S. Popeskou P. Gaffuri G. Lollo L. Ambrosiani F. Radaelli M. Frattini M. Marengo K. Galetti G. Iezzi |
| author_sort | S. De Dosso |
| collection | DOAJ |
| description | Background: Colorectal cancer (CRC) is one of the most prevalent tumour types and a leading cause of cancer-related mortality worldwide. Surgery represents the primary therapeutic option, while advanced cases are typically managed with established chemotherapy protocols, which exhibit variable response rates. Recently, the gut microbiota has been implicated in chemoresistance. Notably, Fusobacterium nucleatum, a commensal bacterium found in the oral cavity, is enriched in CRC tissues and has been shown in experimental models to promote CRC cell proliferation and diminish tumour responsiveness to 5-fluorouracil. Though the administration of metronidazole has effectively reduced F. nucleatum load and overall tumour growth in animal models, its efficacy in decreasing F. nucleatum loads in human CRC has yet to be verified. Aim: This proof-of-concept trial aims to determine the effectiveness of metronidazole in reducing the F. nucleatum load in tissues and its potential detrimental effects on tumour cells and the tumour microenvironment. Trial design: Forty patients newly diagnosed with CRC, for whom surgical resection is planned, will receive metronidazole for 10 days before surgery, which must be scheduled within 3 days following the last administration. Patients who do not receive the treatment for at least 7 days will be deemed ineligible for the study and will be replaced. Fusobacterium nucleatum abundance will be assessed through specific quantitative PCR analysis on genomic DNA extracted from diagnostic biopsies and excised tissues, with comparative analysis. |
| format | Article |
| id | doaj-art-cf04497097b4455eb5e64685ef01cc5c |
| institution | Kabale University |
| issn | 2949-8198 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-cf04497097b4455eb5e64685ef01cc5c2025-08-20T03:31:21ZengElsevierESMO Gastrointestinal Oncology2949-81982025-06-01810016910.1016/j.esmogo.2025.100169Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trialS. De Dosso0D. Christoforidis1E. Merlo2A. Vannelli3S. Popeskou4P. Gaffuri5G. Lollo6L. Ambrosiani7F. Radaelli8M. Frattini9M. Marengo10K. Galetti11G. Iezzi12Department of Medical Oncology, Oncology Institute of Southern Switzerland—EOC, Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Correspondence to: Dr Sara De Dosso, Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Ospedale Regionale di Bellinzona e Valli, Via A. Gallino 12, CH-6500 Bellinzona, Switzerland. Tel: +41-(0)91-811-93-02Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Department of Surgery, Ospedale Regionale di Lugano—EOC, Lugano, SwitzerlandInstitute of Pathology EOC, Locarno, SwitzerlandDepartment of Surgery, Ospedale Valduce, Como, ItalyDepartment of Surgery, Ospedale Regionale di Lugano—EOC, Lugano, SwitzerlandDepartment of Surgery, Ospedale Reginale di Bellinzona e Valli—EOC, Bellinzona, SwitzerlandDepartment of Gastroenterology, Ospedale Reginale di Bellinzona e Valli—EOC, Bellinzona, SwitzerlandDepartment of Pathology, Ospedale Valduce, Como, ItalyDepartment of Gastroenterology, Ospedale Valduce, Como, ItalyDepartment of Laboratory of Genetics and Molecular Pathology, Istituto Cantonale di Patologia EOC, Locarno, SwitzerlandDepartment of Surgery, Ospedale Regionale di Locarno La Carità—EOC, Locarno, SwitzerlandDepartment of Surgery, Ospedale Beata Vergine di Mendrisio—EOC, Mendrisio, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Laboratory for Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandBackground: Colorectal cancer (CRC) is one of the most prevalent tumour types and a leading cause of cancer-related mortality worldwide. Surgery represents the primary therapeutic option, while advanced cases are typically managed with established chemotherapy protocols, which exhibit variable response rates. Recently, the gut microbiota has been implicated in chemoresistance. Notably, Fusobacterium nucleatum, a commensal bacterium found in the oral cavity, is enriched in CRC tissues and has been shown in experimental models to promote CRC cell proliferation and diminish tumour responsiveness to 5-fluorouracil. Though the administration of metronidazole has effectively reduced F. nucleatum load and overall tumour growth in animal models, its efficacy in decreasing F. nucleatum loads in human CRC has yet to be verified. Aim: This proof-of-concept trial aims to determine the effectiveness of metronidazole in reducing the F. nucleatum load in tissues and its potential detrimental effects on tumour cells and the tumour microenvironment. Trial design: Forty patients newly diagnosed with CRC, for whom surgical resection is planned, will receive metronidazole for 10 days before surgery, which must be scheduled within 3 days following the last administration. Patients who do not receive the treatment for at least 7 days will be deemed ineligible for the study and will be replaced. Fusobacterium nucleatum abundance will be assessed through specific quantitative PCR analysis on genomic DNA extracted from diagnostic biopsies and excised tissues, with comparative analysis.http://www.sciencedirect.com/science/article/pii/S294981982500038Xcolon cancerFusobacterium nucleatummetronidazolemicrobiota |
| spellingShingle | S. De Dosso D. Christoforidis E. Merlo A. Vannelli S. Popeskou P. Gaffuri G. Lollo L. Ambrosiani F. Radaelli M. Frattini M. Marengo K. Galetti G. Iezzi Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial ESMO Gastrointestinal Oncology colon cancer Fusobacterium nucleatum metronidazole microbiota |
| title | Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial |
| title_full | Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial |
| title_fullStr | Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial |
| title_full_unstemmed | Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial |
| title_short | Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial |
| title_sort | preoperative metronidazole treatment to evaluate its efficacy in reducing fusobacterium nucleatum colonisation in colorectal cancer patients a proof of concept trial |
| topic | colon cancer Fusobacterium nucleatum metronidazole microbiota |
| url | http://www.sciencedirect.com/science/article/pii/S294981982500038X |
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