Sequencing brain metastases and opportunities for targeted therapies

CNS metastases have long been recognized as a common and late complication of systemic malignancies. They represent the most common tumor of the brain. As outcomes and overall survival improve with better tolerated and more durable responses from therapies for systemic cancers, the incidence and prevalence of brain metastases is likely to increase. Among the most common systemic cancers leading to brain metastases include lung, melanoma, breast (triple-negative histology) and renal cell cancers. To date, there has been infrequent involvement of gastrointestinal and gynecologic malignancies; however, this may also change, reflecting improvement in overall survival and therapeutic regimens. Traditional therapy of brain metastases has focused on surgery, radiation therapy or best supportive/palliative care. The advent of modern genomic techniques, including next-generation and whole-exome sequencing, has allowed for the identification of unique markers and potential drivers of metastatic pathways. This review aims to discuss and highlight the known drivers of disease and the opportunities for ultimate development of targeted therapies.