A kinome-wide CRISPR screen reveals BET inhibition-associated endothelial cell resistance to anti-angiogenic therapy

Abstract

Abstract Angiogenesis inhibition is a useful strategy for treating cancer. However, the efficacy of anti-angiogenic therapy (AAT) in clinical oncology has been limited largely by highly variable patient response and the inevitable occurrence of resistance. The modest patient benefits have underscored a pressing need for qualified biomarkers and better knowledge of resistance mechanisms. Blood endothelial cells (ECs) are one of the main targets of AAT in the tumor microenvironment. Hence, understanding the EC response to AAT will provide insight into tumor response. To identify molecular modifiers of the EC response to AAT (in this study, bevacizumab, a humanized neutralizing a..