Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer.

ABSTRACT:

Background

No targeted drugs are currently available against small cell lung cancer (SCLC). BCL-2 family members are involved in apoptosis regulation and represent therapeutic targets in many malignancies.

Methods

Expression of BCL-2 family members in 27 SCLC cell lines representing all known four SCLC molecular subtypes was assessed by qPCR, Western blot and mass spectrometry-based proteomics. BCL-2 and MCL-1 inhibition (venetoclax and S63845, respectively) was assessed by MTT assay and flow cytometry and in mice bearing human SCLC tumours. Drug interactions were calculated using the Combenefit software. Ectopic BAX overexpression was achieved by expression plasmids.

Results

The highest BCL-2 expression levels were detected in ASCL1- and POU2F3-driven SCLC cells. Alt

SUBMITTER: Valko Z 

PROVIDER: S-EPMC10147697 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature