**1. Introduction**

Lung carcinoma is among the deadliest cancers and its treatment is an important challenge for oncologists. Approximately 16–20% of patients with lung cancer develop brain metastasis, regarded as the most life-threatening complication of the disease. Population-based incidence proportions for brain metastasis are highest for lung cancer (20% against 9.6% for all common cancers) [1]. The frequency of the diagnosis of lung cancer brain metastasis (LCBM) has increased and the reasons for this are not entirely clear. Certainly, advances in radiology have resulted in increased sensitivity for tracing brain metastatic sites. In addition, metastatic tumor cells behind the blood-brain barrier (BBB) are less vulnerable to chemotherapeutic agents ("pharmacologic sanctuary"). Further, there are effects of the increasing age of the population [2]. The incidence and severity of the cerebral symptoms vary from minimal to severely debilitating. Less than 4% of patients with metastatic NSCLC live longer than five years after the diagnosis [3–5]. Obviously, protecting patients from developing brain metastases would significantly alleviate the disease burden and improve outcomes. Knowledge of the subsequent steps tumor cells need to take before growing as metastases in the brain is essential. In this review, we will summarize

current knowledge on the genes and pathways operative in the development of brain metastasis of NSCL and summarize the application of targeted drugs.
