An <i>in silico</i> evaluation of lorlatinib as a potential therapy for novel amino acid substitutions in the tyrosine kinase domain of the ALK protein associated with cancer.

ABSTRACT: The anaplastic lymphoma kinase (alk) gene on chromosome 2 encodes a receptor tyrosine kinase protein essential for key signaling pathways regulating cell proliferation and differentiation. Mutations in alk have been implicated in multiple cancers, including non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma. While ALK inhibitors have demonstrated efficacy in targeted therapies, resistance due to specific amino acid substitutions requires the development of novel therapeutic strategies. This study aims to identify ALK tyrosine kinase domain mutations using data from the Cancer Genome Atlas and to evaluate the potential of lorlatinib, a third-generation ALK inhibitor, in overcoming these mutations. Using the SIFT and Polyphen-2 algorithms, we identifie

SUBMITTER: Zapata Dongo RJ 

PROVIDER: S-EPMC12213726 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature