Pathogenesis-based treatment strategies for brain metastases from non-small cell cancer

More than half of brain metastases (BMs) in patients with non-small cell lung cancer are diagnosed at the time of lung cancer diagnosis and are therefore potentially amenable to systemic treatment. Before the introduction of molecular targeting therapy, medical treatment was thought to be ineffective owing to the presence of the blood-brain barrier (BBB). However, the molecular activities of cancer cells in the central nervous system affect the brain microenvironment, changing the function of the BBB and blood-cerebrospinal fluid barrier, allowing drug delivery. In non-small cell lung cancer with driver gene mutations, BMs respond rapidly to molecular targeted drugs. Although the immune response is attenuated within BMs, it varies according to cancer type. In addition, the changes in immune response after immune checkpoint inhibitor administration vary from patient to patient. In treating BMs, which develop in the unique environment of the brain, it is particularly important to understand these pathologies and develop pathogenesis-based treatment strategies. Although drug therapy is effective against BMs, it is not curative, as BMs will eventually acquire resistance. In the era of molecular targeted agents, it is important to determine the most appropriate combination of treatments for each individual patient, taking into account the effectiveness of conventional local treatments and drug therapy, the presence of side effects, and the timing of their onset.