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In this context, the reported experiments were aimed at verifying a possible interplay between lactate and butyrate in modulating the efficacy of antineoplastic drugs. Butyrate is a product of gut bacterial flora, shown to be endowed with anticancer properties; conversely, increased lactate levels in cancer cells were found to be associated with higher proliferation and drug resistance. For the reported experiments, we adopted two cell lines from clinically relevant, but different cancer forms: pancreatic and triple-negative mammary adenocarcinomas. In spite of their different tissue origin, the two cell lines appeared to similarly respond to the effects of the two metabolites, which were found to modulate in opposite ways the expression of key genes involved in DNA repair by homologous recombination. As a consequence, changed efficacy of this repair pathway and modified response to PARP inhibitors were observed. Notably, our results also suggest that the counteracting effect between these two metabolites may be leveraged to address additional challenges limiting the success of anticancer therapies.<\/jats:p>","DOI":"10.3390\/ijms27031517","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:46:28Z","timestamp":1770137188000},"page":"1517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Metabolites\u2019 Interplay Can Modulate DNA Repair by Homologous Recombination"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-8290","authenticated-orcid":false,"given":"Valentina","family":"Rossi","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Section of General Pathology, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-5206","authenticated-orcid":false,"given":"Mirco","family":"Masi","sequence":"additional","affiliation":[{"name":"Computational and Chemical Biology, Italian Institute of Technology, 16152 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-0107","authenticated-orcid":false,"given":"Marzia","family":"Govoni","sequence":"additional","affiliation":[{"name":"Centre for Applied Biomedical Research (CRBA), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8491-8844","authenticated-orcid":false,"given":"Marina","family":"Veronesi","sequence":"additional","affiliation":[{"name":"Structural Biophysics Facility, Italian Institute of Technology, 16163 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Duca","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Section of General Pathology, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-6675","authenticated-orcid":false,"given":"Stefania","family":"Girotto","sequence":"additional","affiliation":[{"name":"Structural Biophysics Facility, Italian Institute of Technology, 16163 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6370-1176","authenticated-orcid":false,"given":"Andrea","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Computational and Chemical Biology, Italian Institute of Technology, 16152 Genoa, Italy"},{"name":"Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy"},{"name":"Centre Europ\u00e9en de Calcul Atomique et Mol\u00e9culaire (CECAM), Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-0176","authenticated-orcid":false,"given":"Giuseppina","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Section of General Pathology, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s44324-024-00047-w","article-title":"Regulation of gene expression through protein-metabolite interactions","volume":"3","author":"Hornisch","year":"2025","journal-title":"npj Metab. 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