The Stem Cell Niche as a Pharmaceutical Target for Prevention of Skeletal Metastases

John      M. Chirgwin

doi:10.2174/187152012800228797

Abstract

Advanced cancers of the prostate and breast commonly progress by metastasizing to the skeleton, where they are incurable but cause serious morbidity and contribute to mortality. Growth of tumor in bone takes several years, opening a large window for pharmaceutical prevention of metastatic progression. Bone provides a unique microenvironment for tumor growth, including niches occupied by hematopoietic and mesenchymal stem cells. Recent data suggest that circulating tumor cells usurp these niches and compete with the normal stem cell occupants. Agents that encourage normal hematopoiesis or bone formation could inhibit colonization of bone by tumor stem cells and prevent or delay metastatic progression. It may be possible to develop high-throughput assays to test compounds for their ability to suppress tumor stem cell occupation of skeletal niches, thus decreasing metastatic progression in at-risk patients.

Keywords: Bone metastases, Stem cell niche, Hematopoietic niche, Endosteal niche, Mesenchymal cell niche, Prostate cancer, Breast cancer, Anti-resorptive agents, Bone-anabolic agents, SKELETON