BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma.

ABSTRACT:

Background

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives the majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents a potential vulnerability exploitable by senolytic agents.

Methods

We established new patient-derived PA cell lines that preserve molecular features of the primary tumors and can be studied in OIS and proliferation depending on expression or repression of the SV40 large T antigen. We determined expression of anti-apoptotic BCL-2 members in these models and primary PA. Dependence of senescent PA cells on anti-apoptotic BCL-2 members was investigated using a comprehensive

SUBMITTER: Selt F 

PROVIDER: S-EPMC10076946 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature