Targeting FAcilitates Chromatin Transcription complex inhibits pleural mesothelioma and enhances immunotherapy.

ABSTRACT:

Background

Diffuse pleural mesothelioma (DPM) is an aggressive therapy-resistant cancer with unique molecular features. Numerous agents have been tested, but clinically effective ones remain elusive. Herein, we propose to use a small molecule CBL0137 (curaxin) that simultaneously suppresses nuclear factor-κB (NF-κB) and activates tumor suppressor p53 via targeting FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone critical for DNA repair.

Methods

We used DPM cell lines, murine models (xeno- and allo-grafts), plus DPM patient samples to characterize anti-tumor effects of CBL0137 and to delineate specific molecular mechanisms.

Results

We verified that CBL0137 induced cell cycle arrest and apoptosis. We also discovered that DPM is a FACT-dependent ca

SUBMITTER: Singh A 

PROVIDER: S-EPMC10652639 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature