Chapter 2 – The Management and Biology of Metastatic Cancers to the Brain

Brain metastases are a serious consequence of solid tumors that often result in significant morbidity and mortality, with the highest incidence rates in lung cancers and melanoma. In this chapter, we will review the highly specialized structure of the blood–brain-barrier (BBB), which forms to an immunologically distinct space that excludes charged moieties and macromolecules. We will also review how tumor cells interact with the brain microenvironment in order to cross the endothelium of the BBB through the secretion of a variety of molecules implicated in cell invasion. P-glycoprotein (P-gp) also plays an important role in keeping out larger molecules (such as chemotherapeutic agents); current investigations into inhibiting the activity of P-gp will also be discussed. We will demonstrate that when choosing a chemotherapeutic regimen for the management of brain metastases, the decision should be based upon the original histology of the primary tumor, with special consideration regarding the cerebral distribution of the chemotherapeutic agent. In addition, we will discuss several new targeted agents in the treatment of solid malignancies that have been examined in patients with brain metastases.