Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase. Its dysregulation, such as through gene rearrangements, point mutations, or deletions, has oncogenic potential across various tumour types [1]. ALK fusions, like the prevalent EML4-ALK in non-small cell lung cancer (NSCLC), lack normal spatial and temporal regulation, influencing dimerisation and substrate specificity [1].

ALK gene rearrangements are potent oncogenic drivers in malignancies like NSCLC. The discovery of ALK tyrosine kinase inhibitors (TKIs) has improved outcomes for ALK-mutated NSCLC patients, but resistance, both intrinsic and acquired, remains a challenge [2]. Different ALK TKIs are associated with distinct resistance mutation patterns. For instance, the frequency of the ALKG1202R mutation increases after treatment with second-generation agents, and secondary ALK mutations predict sensitivity to the third-generation inhibitor lorlatinib [3]. Sequential use of ALK inhibitors can also select for lorlatinib-resistant compound ALK mutations [4].

In conclusion, ALK is a key oncogenic driver in multiple cancers, especially NSCLC. Research on ALK and its inhibitors has significantly advanced treatment for ALK-positive patients. Understanding ALK's role in tumour biology through functional studies, including those on resistance mechanisms, is crucial for further optimising therapeutic strategies for ALK-positive diseases.