Protective autophagy decreases lorlatinib cytotoxicity through Foxo3a-dependent inhibition of apoptosis in NSCLC.

ABSTRACT: Lorlatinib is a promising third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has been approved for treating ALK-positive non-small-cell lung cancer (NSCLC) patients with previous ALK-TKI treatment failures. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A more comprehensive understanding of the acquired resistance mechanisms to lorlatinib will enable the development of more efficacious therapeutic strategies. The efficacy of chloroquine (CQ) in combination with lorlatinib in ALK-positive NSCLC cells in vitro and in vivo was assessed using CCK-8, colony formation, immunofluorescence staining, flow cytometry analysis, western blot analysis, and xenograft implantation. Here, we show that lorlatinib induced apoptosis

SUBMITTER: Lu C 

PROVIDER: S-EPMC9033765 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature