Efficacy of Incremental Next-Generation ALK Inhibitor Treatment in Oncogene-Addicted, ALK-Positive, TP53-Mutant NSCLC.

ABSTRACT: The anaplastic lymphoma kinase (ALK) gene fusion rearrangement is a potent oncogene, accounting for 2-7% of lung adenocarcinomas, with higher incidence (17-20%) in non-smokers. ALK-positive tumors are sensitive to ALK tyrosine kinase inhibitors (TKIs), thus ALK-positive non-small-cell lung cancer (NSCLC) is currently spearheading precision medicine in thoracic oncology, with three generations of approved ALK inhibitors in clinical practice. However, these treatments are eventually met with resistance. At the molecular level, ALK-positive NSCLC is of the lowest tumor mutational burden, which possibly accounts for the high initial response to TKIs. Nevertheless, TP53 co-mutations are relatively frequent and are associated with adverse outcome of crizotinib treatment, whereas utility of next-

SUBMITTER: Urban L 

PROVIDER: S-EPMC7563786 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature