Beyond the brain: exploring the impact of animal models of leptomeningeal disease from solid tumors.

Leptomeningeal disease (LMD) is a devastating manifestation of late-stage cancer which currently suffers from a lack of effective therapeutics. Unfortunately, a significant obstacle preventing the widespread development and testing of therapeutics for LMD is the lack of biologically accurate animal models. We provide overviews of six types of animal models of leptomeningeal metastasis from solid tumors: injection of tumor cells into the cerebrospinal fluid (CSF), blood, or brain parenchyma; subcutaneous or mammary fat pad injection of tumor cells; the LeptoM/LM-phenotype model; and genetic manipulation. We identify the pros and cons of each model and suggest broad areas of future research that could improve each model in terms of its similarity to human LMD.