Inhibition of the anti-apoptotic protein BCL2 in EML4-ALK cell models as a second proposed therapeutic target for non-small cell lung cancer.

ABSTRACT: The anaplastic lymphoma kinase (ALK) oncoprotein plays a crucial role in non-small cell lung cancer (NSCLC) by activating signaling pathways involved in cell proliferation and survival through constitutive phosphorylation. While first-line crizotinib can regulate phosphorylation, mutations in the ALK gene can lead to resistance against ALK inhibitors (ALKi) such as ceritinib and alectinib. On the other hand, overexpression of BCL2, a protein involved in cell death regulation, has been observed in NSCLC and is considered a potential therapeutic target. In this study, we propose to inhibit BCL2 as a secondary therapeutic target in EML4-ALK cell models to overcome resistance caused by ALK mutations. Four Ba/F3 EML4-ALK cell models (WT, C1156Y, L1196M, and G1202R) generated by site-directed mu

SUBMITTER: Zapata Dongo RJ 

PROVIDER: S-EPMC11750102 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature