Sepanotronium Bromide (YM155) is a drug that targets the action of survivn (apoptosis inhibitor) in triple-negative breast cancer. In pre-clinical studies YM155 was shown to be a very potent drug for treating cancer.

However, the drug failed in clinical trials due to emergence of resistance.

YM155
                      Drug Resistance to YM155


We set out to understand the transcriptional level mechanisms that regulate emergence of drug resistance to YM155. We performed gene set enrichment analysis using RNA seq data for comparison of sensitive and resistant cell lines. Using this we identify upregulated and downregulated genes implicated in resistance to YM155. Next we build a kinase network to understand the important pathways mediating this response. We also identify top 10 drugs that can reverse the cell signature using cMAP analysis.


Our next goal is to experimentally validate these results

 

PI
Dr. Anindita Chakrabarty
Place
Shiv Naadar University, India
Project Duration
Started in Aug 2020