Molecular Pathways Molecular Pathways: Niches in Metastatic Dormancy

Despite the best available treatments for primary tumors, cancer can return, even after a long disease-free interval. During this period, cancer cells are believed to lie dormant in either primary sites, metastatic sites, or independent sites like bone marrow, effectively escaping adjuvant cytotoxic treatments. To date, little is known about how these cells transition to dormancy, or how they are reactivated if cancer recurs. Recent studies have revealed the effects of tumormicroenvironment or niche on the regulation of tumor dormancy via the signaling pathways of growth arrest–specific 6, bonemorphogenetic protein 7, and TGFb1, and that the balance between activation of p38MAPK and ERKMAPK plays a pivotal role in tumor dormancy. In this review, we discuss tumor dormancy from the perspective of the niche and consider potential therapeutic targets. Greater understanding of themechanisms involvedwill help guide innovation in the care of patients with advanced cancer. Clin Cancer Res; 20(13); 3384–9. 2014 AACR.