ArticleCell reports. Medicine2024
Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases.
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Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3citing papers in PubMed
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3 citing papers in PubMed, 7 citations in OpenAlex.
- Metastatic organotropism in peritoneal metastasis: Paget's hypothesis revisited.Clinical and experimental medicine · 2026Review
- Proteomics analysis reveals progesterone receptor induced mitochondria-mediated apoptosis in breast cancer cells.Scientific reports · 2025Article
- Modeling oxaliplatin resistance in colorectal cancer reveals a SERPINE1-based gene signature (RESIST-M) and therapeutic strategies for pro-metastatic CMS4 subtype.Cell death & disease · 2025Article
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Authors and funding
36 authors at 10 institutions in 1 country.
Sanne BootsmaAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
Mark P G DingsAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
Job KesselaarAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
Roxan F C P A HeldermanAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Department of Radiation Oncology, Amsterdam, the Netherlands.
Kyah van MegesenLaboratory of Translational Oncology, UMC Utrecht Cancer Center, Utrecht, the Netherlands.
Alexander ConstantinidesLaboratory of Translational Oncology, UMC Utrecht Cancer Center, Utrecht, the Netherlands.
Leandro Ferreira MorenoAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Ellen StellooDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Enzo M ScutiglianiCancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Department of Medical Biology, Amsterdam, the Netherlands.
Bella BokanAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Department of Radiation Oncology, Amsterdam, the Netherlands.
Arezo TorangAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Sander R van HooffAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Danny A ZwijnenburgAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Valérie M WoutersAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Vincent C J van de VlasakkerDepartment of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
Laskarina J K GalanosDepartment of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
Lisanne E NijmanAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Adrian LogiantaraAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Veronique L VeenstraAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Sophie SchlingemannAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Sterre van PiggelenLaboratory of Translational Oncology, UMC Utrecht Cancer Center, Utrecht, the Netherlands.
Nicole van der WelAmsterdam UMC Location University of Amsterdam, Electron Microscopy Center, Amsterdam, the Netherlands.
Przemek M KrawczykCancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Department of Medical Biology, Amsterdam, the Netherlands.
Johannes J PlatteeuwAvivia Projects BV, Boxtel, the Netherlands.
Jurriaan B TuynmanAmsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands.
Ignace H de HinghDepartment of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
Jan P G KlompLead Pharma, Oss, the Netherlands.
Arthur OubrieLead Pharma, Oss, the Netherlands.
Petur SnaebjornssonDepartment of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Jan Paul MedemaAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Arlene L OeiAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Department of Radiation Oncology, Amsterdam, the Netherlands.
Onno KranenburgLaboratory of Translational Oncology, UMC Utrecht Cancer Center, Utrecht, the Netherlands.
Clara C ElbersAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Kristiaan J LenosAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Louis VermeulenAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
Maarten F BijlsmaAmsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands. Electronic address: m.f.bijlsma@amsterdamumc.nl.
Oncode Institute · NLCancer Genomics Centre · NLAmsterdam Neuroscience · NLAmsterdam University Medical Centers · NLRadboud University Nijmegen · NLAkzoNobel (Netherlands) · NLThe Netherlands Cancer Institute · NLUniversity of Amsterdam · NLUtrecht University · NLVrije Universiteit Amsterdam · NL
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery in resectable patients shows limited benefit, and novel treatments are urgently needed. The majority of CRC-PMs represent the CMS4 molecular subtype of CRC, and here we queried the vulnerabilities of this subtype in pharmacogenomic databases to identify novel therapies. This reveals the copper ionophore elesclomol (ES) as highly effective against CRC-PMs. ES exhibits rapid cytotoxicity against CMS4 cells by targeting mitochondria. We find that a markedly reduced mitochondrial content in CMS4 cells explains their vulnerability to ES. ES demonstrates efficacy in preclinical models of PMs, including CRC-PMs and ovarian cancer organoids, mouse models, and a HIPEC rat model of PMs. The above proposes ES as a promising candidate for the local treatment of CRC-PMs, with broader implications for other PM-prone cancers.
Indexed as
Colorectal NeoplasmsMitochondriaPeritoneal NeoplasmsAnimalsCell Line, TumorFemaleHumansHyperthermic Intraperitoneal ChemotherapyMiceRatscopperelesclomolHIPECmesenchymal cancer cellmitochondriamolecular subtypeoxidative phosphorylationperitoneal metastases
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.