Targeting mitotic exit in solid tumors.

ABSTRACT: Targeting mitosis by taxanes is one of the most common chemotherapeutic approaches in various malignant solid tumors, but cancer cells may survive antimitotic treatment with attainable in vivo concentrations due to mitotic slippage with a residual activity of the ubiquitin ligase anaphase-promoting complex (APC/C) and a continuous slow ubiquitin-proteasome-dependent cyclin B-degradation leading to mitotic exit. Therefore, blocking cyclin B-proteolysis via additional proteasome (PI) or APC/C-inhibition may have the potential to enhance tumor cell eradication by inducing a more robust mitotic block and mitotic cell death. Here, we analyzed this approach in different cell lines and more physiological patient-derived xenografts (PDX) from lung and breast cancer. The sequential combinati

SUBMITTER: Greil C 

PROVIDER: S-EPMC8332852 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature