YM155 Induces DNA Damage and Cell Death in Anaplastic Thyroid Cancer Cells by Inhibiting DNA Topoisomerase IIa at the ATP-Binding Site

Anaplastic thyroid cancer (ATC) is among the most aggressive of human cancers, and currently there are few effective treatments for most patients. YM155, first identified as a survivin inhibitor, was highlighted in a high-throughput screen performed by the National Cancer Institute, killing ATC cells in vitro and in vivo. However, there was no association between survivin expression and response to YM155 in clinical trials, and YM155 has been mostly abandoned for development despite favorable pharmacokinetic and toxicity profiles. Currently, alternative mechanisms are being explored for YM155 by a number of groups. In this study, ATC patient samples show overexpression of topoisom

Automated summary

Anaplastic thyroid cancer (ATC) is a highly aggressive form of cancer with few effective treatment options. YM155, previously identified as a survivin inhibitor, showed promise in killing ATC cells in laboratory and animal studies. However, clinical trials did not show a correlation between survivin expression and response to YM155. Despite this setback, alternative mechanisms for YM155 are currently being investigated.