Advances in the treatment of brain metastases in EGFR-mutant non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the predominant subtype of lung cancer, and brain metastasis (BM) is a frequent and serious complication that significantly impacts patients’ survival and quality of life. EGFR mutations play a crucial role in the progression of NSCLC, particularly the Ex19del and L858R mutations. This paper comprehensively explores the pathological mechanisms of BM in EGFR-mutant NSCLC, covering key aspects such as tumor cell invasion, epithelial-mesenchymal transition (EMT), exosome secretion, and blood–brain barrier (BBB) disruption. It also discusses the classification of EGFR mutations and the strategies used in targeted therapy. Notably, third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), like osimertinib, have shown remarkable efficacy in treating BM. The paper further explores the potential of combination therapy, immunotherapy, and local treatment options. Despite significant progress, drug resistance mechanisms remain complex. The development of fourth-generation EGFR-TKIs and antibody-drug conjugates (ADCs) offers new solutions to overcome resistance. In addition, dynamic monitoring of circulating tumor DNA (ctDNA) and analysis of cerebrospinal fluid (CSF) can facilitate the early detection of molecular progression and guide precision treatment decisions. In the future, it is essential to optimize combination therapy strategies through multi-disciplinary collaboration, integrating genomics, imaging, and clinical characteristics to enhance efficacy and safety, improve clinical practice, and ultimately elevate patients’ quality of life.