Aryl hydrocarbon receptor nuclear translocator-like (ARNTL/BMAL1) is associated with bevacizumab resistance in colorectal cancer via regulation of vascular endothelial growth factor A.

ABSTRACT:

Background

The identification of new biomarkers and the development of novel, targetable contexts of vulnerability are of urgent clinical need in drug-resistant metastatic colorectal cancer (mCRC). Aryl-Hydrocarbon-Receptor-Nuclear-Translocator-Like (ARNTL/BMAL1) is a circadian clock-regulated transcription factor promoting expression of genes involved in angiogenesis and tumour progression. We hypothesised that BMAL1 increases expression of the vascular endothelial growth factor A VEGFA gene and, thereby, confers resistance to anti-angiogenic therapy with bevacizumab (Beva), a clinically used antibody for neutralization of VEGFA.

Methods

PCR and immunohistochemistry were employed to assess BMAL1 expression in mice (C57BL/6 J ^Apcmin/+; BALB/c ^nu/nu xeno

SUBMITTER: Burgermeister E 

PROVIDER: S-EPMC6642438 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature