Xuebing Zhang,1,* Xia Zhang,1,2,* Hang Yin,1 Qizheng Li,1 Buqun Fan,1 Bolun Jiang,1 Anqi Xie,1 Dandan Guo,1 Huanling Hao,3 Bin Zhang1 

1Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Oncology, Dalian Fifth People’s Hospital, Dalian, Liaoning, People’s Republic of China; 3Department of Oncology, Dandong First Hospital, Dandong, Liaoning, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bin Zhang; Huanling Hao, Email Zhangbin_dlmu@163.com; 1123088162@qq.com

Abstract: Lung cancer is a malignant tumor with high morbidity and mortality in China and worldwide. Once it metastasizes to the brain, its prognosis is very poor. Brain metastases are found in about 20% of newly diagnosed non-small-cell lung cancer (NSCLC) patients. About 30% of NSCLC patients develop brain metastases during treatment. NSCLC that is positive for EGFR, ALK, and ROS1 variations is especially likely to metastasize to the brain. SPOCK1 is a proteoglycan with systemic physiological functions. It regulates the self-renewal of brain metastasis–initiating cells, regulates invasion and metastasis from the lung to the brain, plays an important role in tumor progression and treatment resistance, and has higher expression in metastatic tumor tissues than other tissues. Current treatments for NSCLC brain metastases include surgery, whole-brain radiotherapy, stereotactic radiotherapy, targeted therapy, and chemotherapy. SPOCK1 is involved in many signaling pathways, by which it influences a variety of NSCLC treatment methods. In this paper, the progress of research on the treatment of NSCLC brain metastases is reviewed to guide decisions on treatment options in clinical practice.

Keywords: SPOCK1, non—small cell lung cancer, NSCLC, brain metastasis, chemotherapy, targeted therapy, immunotherapy