New Publication: Stromal Senescence following Treatment with the CDK4/6 Inhibitor Palbociclib Alters the Lung Metastatic Niche and Increases Metastasis of Drug-Resistant Mammary Cancer Cells

Posted in Cancer Cell Biology Program News

New Publication: Anna T. Riegel, et al.

CDK4/6 inhibitors (CDKis) are a first-line treatment for metastatic hormone-receptor-positive breast cancer, but resistance frequently develops. One potential resistance mechanism could be induction of cellular senescence in non-tumor tissues. The aim of our study was to identify CDKi-induced changes to host tissues that impact metastasis. Using mouse models, we found that pretreatment with palbociclib can increase metastatic seeding of CDKi-resistant mammary cancer cells in lungs and that this can be mitigated by eliminating senescent host cells. We describe palbociclib-induced gene expression changes in lungs that correlate with this effect and reveal altered intra-lung immune populations. Senescent endothelial cells are identifiable within lung metastases of mice pretreated with palbociclib. Palbociclib-treated primary endothelial cell lines become senescent and increase tumor cell migration and monocyte trans-endothelial invasion. These studies describe how CDKi-induced cellular senescence in host tissues could affect metastasis in breast cancer, which remains a key obstacle to achieving long-term survival.

Cancers 202315(6), 1908;