Figure 1.

Schematic illustrating pathophysiological aspects of metastasis to the brain. Brain metastasis is an inefficient process marked by high rates of cellular attrition, and impacted by a myriad of selection pressures that drive clonal evolution. This includes requirements intrinsic to the metastatic cascade (capabilities for “metastatic fitness” are indicated in horizontal tracks) as well as extrinsic factors that drive the selection of particular tumor cell clones able to successfully establish brain metastases (vertical tracks; e.g., chemotherapy, radiotherapy or surgery) (adapted from [46]).