biostudies-literatureUnknown27(1)Perkins DWBreast Cancer NowDisseminated tumor cells frequently exhibit a period of dormancy, rendering them chemotherapy insensitive; conversely, the systemic delivery of chemotherapies can result in normal tissue damage. Using multiple mouse and human breast cancer models, we demonstrate that prior chemotherapy administration enhances metastatic colonization and outgrowth. <i>In vitro</i>, chemotherapy-treated fibroblasts display a pro-tumorigenic senescence-associated secretory phenotype (SASP) and are effectively eliminated by targeting the anti-apoptotic protein BCL-xL. <i>In vivo</i>, chemotherapy treatment induces SASP expression in normal tissues; however, the accumulation of senescent cells is limited, and BCL-xL inhibitors are unable to reduce chemotherapy-enhanced metastasis. This likely reflects that chemiScience108503https://www.ebi.ac.uk/biostudies/studies/S-EPMC10755366biostudies-literatureTherapy-induced normal tissue damage promotes breast cancer metastasis.PMC10755366Perkins DWBuus RSteiner IRobertson DO'Leary LHaider SIsacke CMfalseTherapy-induced normal tissue damage promotes breast cancer metastasis.Disseminated tumor cells frequently exhibit a period of dormancy, rendering them chemotherapy insensitive; conversely, the systemic delivery of chemotherapies can result in normal tissue damage. Using multiple mouse and human breast cancer models, we demonstrate that prior chemotherapy administration enhances metastatic colonization and outgrowth. <i>In vitro</i>, chemotherapy-treated fibroblasts display a pro-tumorigenic senescence-associated secretory phenotype (SASP) and are effectively eliminated by targeting the anti-apoptotic protein BCL-xL. <i>In vivo</i>, chemotherapy treatment induces SASP expression in normal tissues; however, the accumulation of senescent cells is limited, and BCL-xL inhibitors are unable to reduce chemotherapy-enhanced metastasis. This likely reflects that chem2024-01-01T00:00:00Z2024 Jan2026-05-28T20:08:29.044Z2025-04-04T03:20:43.124ZS-EPMC107553663816142610.1016/j.isci.2023.108503