Abstract: Anaplastic lymphoma kinase (ALK ) rearrangement is extremely rare in lung squamous cell carcinoma (LSCC), and it remains controversial as to whether LSCC patients with ALK  rearrangement can benefit from ALK tyrosine kinase inhibitors (TKIs). Here, we report an LSCC patient with ALK  rearrangement who was treated with sequential ALK TKI therapies and experienced a clinical benefit of 35 months. Although the use of ALK TKIs showed clinical benefits, targeted next-generation sequencing (NGS) for dynamic monitoring of circulating tumor DNA (ctDNA) from patient plasma revealed the accumulation of ALK  resistance mutations, which could provide valuable information in designing the treatment strategy. Our study highlights the importance of dynamic monitoring of ctDNA using NGS to discover tumor evolution to guide treatment decision-making and provides meaningful insights into the potential treatment options for ALK -positive LSCC patients.
Keywords: ALK  rearrangement, dynamic monitoring, resistance mutation, next-generation sequencing