# A Case Report of Acquired ALK Fusion in ALK Wild‐Type Lung Adenocarcinoma Following Chemotherapy and a Literature Review Is Presented

## TL;DR

A patient with lung cancer initially negative for ALK fusion later developed it after chemotherapy, suggesting treatment may select for ALK-positive tumor cells.

## Contribution

This case report presents a rare instance of acquired ALK fusion in lung adenocarcinoma following chemotherapy.

## Key findings

- ALK fusion was detected after disease progression following chemotherapy in a patient initially ALK-negative.
- Switching to ALK inhibitor alectinib led to a partial response, indicating the clinical relevance of repeat genetic testing.
- Chemotherapy may exert selective pressure that enriches ALK fusion-positive tumor clones.

## Abstract

ALK fusion is a key driver mutation in non‐small cell lung cancer, typically present as a primary genetic alteration. This article reports a rare case of a patient who was initially ALK‐negative but subsequently developed an ALK fusion following chemotherapy. A 52‐year‐old female was diagnosed with advanced lung adenocarcinoma. Initial genetic testing showed wild‐type EGFR and ALK. She received first‐line platinum‐based doublet chemotherapy combined with a VEGF inhibitor and a PD‐L1 inhibitor, achieving a partial response. Upon disease progression, repeat genetic testing unexpectedly detected an ALK fusion. Treatment was then switched to the ALK inhibitor alectinib, and the patient again achieved a partial response. This case suggests that chemotherapy may enrich ALK fusion‐positive tumour cell clones through selective pressure. These findings highlight the clinical importance of repeated genetic testing after disease progression and provide new insights for post‐resistance treatment strategies.

This report presents a rare case of ALK fusion emerging after chemotherapy and discusses its potential mechanisms and clinical implications.