Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story.

Lung cancer is the most common primary tumor associated with brain metastases. Currently, the molecular mechanisms underlying the pathogenesis of lung cancer brain metastasis (LCBM) have not been fully elucidated and effective therapeutic strategies for treating this disease are still lacking. The blood-brain barrier (BBB) is a selectively permeable membrane and is crucial in maintaining brain homeostasis. Increasing evidence from clinical and pre-clinical studies indicated that metastatic circulating tumor cells from lung cancer can affect the cellular biology of BBB components, and destruct its integrity as well as function to penetrate the BBB to clone in the brain parenchyma, therein producing malignant secondary tumors. Therefore, in this review, we aim to discuss about the involvement of BBB alterations during the initiation of LCBM and the cellular and molecular mechanisms underlying. A better understanding of these pathophysiological processes may help open avenues to develop new therapeutic strategies to prevent or treat this notorious disease.