Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma.

ABSTRACT:

Objective

Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial.

Methods

Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation.

Results

Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interesting

SUBMITTER: Song S 

PROVIDER: S-EPMC9720890 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature