Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, with genetic- and protein-based diagnostics playing a crucial role in disease detection and improving patient outcomes. Glycosylation, a major post-translational modification, has recently emerged as a factor influencing cancer progression, immune evasion, and therapeutic resistance. Aberrant glycosylation patterns, particularly among receptor tyrosine kinases (RTKs), have been shown to modulate oncogenic signaling pathways and influence tumor growth. This review provides a comprehensive overview of how glycosylation alterations affect the stability, function, and therapeutic targeting of key RTKs relevant in lung adenocarcinoma: Epidermal growth factor receptor, human epidermal growth factor receptor 2, and cellular mesenchymal-epithelial transition factor, rearranged during transfection, anaplastic lymphoma kinase, and ROS proto-oncogene 1 receptor tyrosine kinase. Despite substantial advances in targeted therapies, initial and acquired resistance remain a major challenge in the treatment of lung cancer. There is growing evidence that strategies targeting glycosylation can be combined with established treatment protocols to help overcome resistance. Finally, we propose future directions for the advancement of glycosylation-based approaches to improve precision medicine.