Anaplastic thyroid cancer (ATC) is among the most aggressive erase Top2a compared with benign thyroid samples and to of human cancers, and currently there are few effective treatments differentiated thyroid cancers. ATC cell lines that overexpress for most patients. YM155, first identified as a survivin inhibitor, Top2a are more sensitive to YM155. We created a YM155-was highlighted in a high-throughput screen performed by the resistant cell line, which shows decreased expression of Top2a National Cancer Institute, killing ATC cells in vitro and in vivo. and is resensitized with Top2a overexpression. Molecular model-However, there was no association between survivin expression ing predicts binding for YM155 in the Top2a ATP-binding site and response to YM155 in clinical trials, and YM155 has been and identifies key amino acids for YM155–Top2a interaction. A mostly abandoned for development despite favorable pharmacoTop2a mutant abrogates the effect of YM155, confirming the kinetic and toxicity profiles. Currently, alternative mechanisms contribution of Top2a to YM155 mechanism of action. Our are being explored for YM155 by a number of groups. In this results suggest a novel mechanism of action for YM155 and may study, ATC patient samples show overexpression of topoisomrepresent a new therapeutic approach for the treatment of ATC.
ASJC Scopus subject areas
- Cancer Research