{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:22:53Z","timestamp":1791084173772,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NewG Lab Pharma, Inc.","award":["SNSF 31003A_163232\/1"],"award-info":[{"award-number":["SNSF 31003A_163232\/1"]}]},{"name":"NewG Lab Pharma, Inc.","award":["KF.S.-4727-02-2019"],"award-info":[{"award-number":["KF.S.-4727-02-2019"]}]},{"name":"KoDiscovery, LLC","award":["SNSF 31003A_163232\/1"],"award-info":[{"award-number":["SNSF 31003A_163232\/1"]}]},{"name":"KoDiscovery, LLC","award":["KF.S.-4727-02-2019"],"award-info":[{"award-number":["KF.S.-4727-02-2019"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SNSF 31003A_163232\/1"],"award-info":[{"award-number":["SNSF 31003A_163232\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["KF.S.-4727-02-2019"],"award-info":[{"award-number":["KF.S.-4727-02-2019"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss Cancer Research","award":["SNSF 31003A_163232\/1"],"award-info":[{"award-number":["SNSF 31003A_163232\/1"]}]},{"name":"Swiss Cancer Research","award":["KF.S.-4727-02-2019"],"award-info":[{"award-number":["KF.S.-4727-02-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Reprogramming of the cellular metabolism is a hallmark of cancer, offering therapeutic opportunities to target cancer cell vulnerabilities for therapeutic purposes. 3-Bromopyruvate (3BP) is a small alkylating agent that functions as an anti-metabolite, targeting key substrates in cancer metabolism and demonstrating antitumor activity across multiple cancer types. However, unformulated 3BP is associated with significant toxicity. This study investigates the efficacy of KAT\/3BP, a clinical derivative of 3BP currently in phase 1 trials for hepatocellular carcinoma, in preclinical lymphoma models. Results: In vitro, KAT\/3BP exhibited cytotoxic activity across 12 lymphoma cell lines\u2014including diffuse large B-cell lymphoma and mantle cell lymphoma\u2014with a median IC50 of 3.7 \u03bcM. It also remained effective against lymphoma cell lines with acquired resistance to FDA-approved therapies. In vivo, treatment with KAT\/3BP led to reduced tumor size in a syngeneic mouse model, with the combination of oral and intratumoral administration showing the greatest efficacy. Furthermore, KAT\/3BP demonstrated synergistic activity when combined with standard lymphoma therapies such as bendamustine and R-CHOP. Conclusions: Our findings highlight the potential of KAT\/3BP as a novel therapeutic option, either as a single agent or in combination regimens, for treating lymphomas.<\/jats:p>","DOI":"10.3390\/cancers17122034","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T05:30:42Z","timestamp":1750224642000},"page":"2034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["KAT\/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4394-7742","authenticated-orcid":false,"given":"Chiara","family":"Tarantelli","sequence":"first","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-1568","authenticated-orcid":false,"given":"Filippo","family":"Spriano","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-8372","authenticated-orcid":false,"given":"Elisa","family":"Civanelli","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7893-1740","authenticated-orcid":false,"given":"Luca","family":"Aresu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Turin, 10095 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Risi","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9551-7122","authenticated-orcid":false,"given":"Eleonora","family":"Cannas","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-2463","authenticated-orcid":false,"given":"Omar","family":"Kayali","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4606-0637","authenticated-orcid":false,"given":"Luciano","family":"Cascione","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3123-6203","authenticated-orcid":false,"given":"Alberto J.","family":"Arribas","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Stathis","sequence":"additional","affiliation":[{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young H.","family":"Ko","sequence":"additional","affiliation":[{"name":"KoDiscovery, LLC, IMET\/Columbus Center, Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5637-8983","authenticated-orcid":false,"given":"Francesco","family":"Bertoni","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5537","DOI":"10.1158\/1078-0432.CCR-12-2587","article-title":"Targeting Cancer Metabolism","volume":"18","author":"Teicher","year":"2012","journal-title":"Clin. 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