Advances in Lung Cancer Driver Genes Associated With Brain Metastasis

Abstract

Brain metastasis, one of the common complications of lung cancer, is an important cause of death in patients with advanced cancer, despite progress in treatment strategies. Lung cancers with positive driver genes have higher incidence and risk of brain metastases, suggesting that driver events associated with these genes might be biomarkers to detect and prevent disease progression. Common lung cancer driver genes mainly encode receptor tyrosine kinases (RTKs), which are important internal signal molecules that interact with external signals. RTKs and their downstream signal pathways are crucial for tumor cell survival, invasion, and colonization in the brain. In addition, new tumor driver genes, which also encode important molecules closely related to the RTK signaling pathway, have been found to be closely related to the brain metastases of lung cancer. In this article, we reviewed the relationship between lung cancer driver genes and brain metastasis, and summarized the mechanism of driver gene-associated pathways in brain metastasis. By understanding the molecular characteristics during brain metastasis, we can better stratify lung cancer patients and alert those at high risk of brain metastasis, which helps to promote individual therapy for lung cancer.

Keywords: brain metastasis; colonization; driver gene; epithelial-mesenchymal transition; lung cancer; receptor tyrosine kinase.

Figure 1

Three studies have shown that the most common type of lung cancer driver gene mutation is EGFR mutation, followed by KRAS mutation and ALK fusion mutation. The black area indicates the percentage of brain metastases in the total number of corresponding mutations. (A) n = 271; (B) n = 227; (C) n = 552. The incidence of brain metastases in patients with driver gene mutations is shown in brackets.

Figure 2

Signaling pathway and mechanism related to lung cancer driver gene in brain metastasis. (A–C) represent the tumor cell survival, EMT, and colonization respectively. (D) corresponds to the cell or molecule in (A–C).