MicroRNAs in brain metastases: big things come in small packages

Metastatic brain tumors provide a formidable obstacle in the survival of affected cancer patients, an obstacle that current treatment is essentially ineffective against. Our understanding of the metastatic cascade has demonstrated the role of incorrectly regulated protein expression and proved it to be a crucial component of this process. Recently, molecular studies have emphasized the role of microRNAs, small non-coding RNAs that alter protein expression, in the regulation of both normal and abnormal biological processes, including cancer and its metastasis to the brain. Furthermore, studies have demonstrated the ability to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on microRNA profiles. Interestingly, manipulation of microRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy, and individually directed therapy, using microRNA in the treatment of metastatic brain tumors may prove very useful. In this review, we focus on the multiple potential microRNA targets for the treatment of metastatic brain lesions as well as current and future directions for its use in gene therapy.