Acquired ALK Resistance Mutations Identified from Liquid Biopsy in an ALK-Rearranged Squamous Cell Lung Cancer Patient Treated with Sequential ALK TKI Therapy: A Case Report

Abstract

Bin Yao,1 Xue Han,2 Linrong Pang,1 Caihong Xu,1 Sisi Liu,2 Xiaochun Cheng,1 Jun Chen1 1Department of Radiotherapy and Chemotherapy, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Research and Development, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaochun Cheng; Jun ChenDepartment of Radiotherapy and Chemotherapy, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of ChinaTel [phone]; [phone]Email [email protected] [email protected]: 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

Keywords

• alk rearrangement
• dynamic monitoring
• resistance mutation
• next-generation sequencing