Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma.

ABSTRACT:

Background

Neuroblastoma is a paediatric cancer that is characterised by poor prognosis for chemoresistant disease, highlighting the need for better treatment options. Here, we asked whether BH3-mimetics inhibiting BCL2 proteins may eliminate chemoresistant neuroblastoma cells.

Methods

We utilised cisplatin-adapted neuroblastoma cell lines as well as patient tissues before and after relapse to study alterations of BCL2 proteins upon chemoresistance.

Results

In a direct comparison of cisplatin-resistant cells we identified a prominent loss of sensitivity to BCL2/BCL-X_L inhibitors that is associated with an increase in MCL1 dependency and high expression of MCL1 in patient tumour tissues. Screening of FDA-approved anti-cancer drugs in chemoresistant cells ide

SUBMITTER: Jacob M 

PROVIDER: S-EPMC10646009 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature