Therapy-induced normal tissue damage promotes breast cancer metastasis.

ABSTRACT: 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. In vitro, chemotherapy-treated fibroblasts display a pro-tumorigenic senescence-associated secretory phenotype (SASP) and are effectively eliminated by targeting the anti-apoptotic protein BCL-xL. In vivo, 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 chem

SUBMITTER: Perkins DW 

PROVIDER: S-EPMC10755366 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature