Rewiring the Niche: Sympathetic Neuropathy Drives Malignant Niche Transformation

In recent years, it has become increasingly evident that hematological malignancies can alter their microenvironment, but the therapeutic implications of these changes and potential targets have not been well characterized. Recent findings now describe how sympathetic neuropathy can drive malignant transformation of the hematopoietic stem cell niche in hematopoietic malignancies

E-Selectin and SDF-1 regulate metastatic trafficking of breast cancer cells within the bone

E-selectin is a key mediator of breast cancer cell (BCC) metastatic entry into the bone and stromal-derived factor 1 (SDF-1) is a critical molecular anchor for BCCs within discrete pro-dormancy bone marrow (BM) niches. Small-molecule inhibitors blocked metastatic entry and mobilized established disease from BM, suggesting a new treatment strategy to prevent breast cancer relapse

Salting the soil: targeting the microenvironment of brain metastases

Paget’s ‘seed and soil’ hypothesis of metastatic spread has acted as a foundation of the field for over a century, with continued evolution as mechanisms of the process have been elucidated. The CNS presents a unique soil through this lens, relatively isolated from peripheral circulation and immune surveillance with distinct cellular and structural composition. Research in primary and metastatic brain tumors has demonstrated that this tumor microenvironment (TME) plays an essential role in the growth of CNS tumors. In each case, the cancerous cells develop complex and bi-directional relationships that reorganize the local TME and reprogram the CNS cells, including endothelial cells, pericytes, astrocytes, microglia, infiltrating monocytes, and lymphocytes. These interactions create a structurally and immunologically permissive TME with malignant processes promoting positive feedback loops and systemic consequences. Strategies to interrupt interactions with the native CNS components, on 'salting the soil,' to create an inhospitable environment are promising in the preclinical setting. This review aims to examine the general and specific pathways thus far investigated in BrM and related work in glioma to identify targetable mechanisms that may have general application across the spectrum of intracranial tumors