Therapy-induced normal tissue damage promotes breast cancer metastasis
Douglas W. Perkins, Ivana Steiner, Syed Waqar Haider, David Robertson, Richard Buus, Lynda O’Leary, Clare M. Isacke
Abstract
, 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 chemotherapy-exposed stromal cells do not enter a BCL-xL-dependent phenotype or switch their dependency to other anti-apoptotic BCL-2 family members. This study highlights the role of the metastatic microenvironment in controlling outgrowth of disseminated tumor cells and the need to identify additional approaches to limit the pro-tumorigenic effects of therapy-induced normal tissue damage.
Topics & Concepts
Breast cancerChemotherapyMetastasisCancer researchMedicineHuman breastBreast cancer metastasisCancerSystemic administrationPathologyOncologyInternal medicineBiologyCancer metastasisIn vivoBiotechnologyCancer Cells and MetastasisImmunotherapy and Immune ResponsesTelomeres, Telomerase, and Senescence