Understanding cancer using small molecule anti-cancer drugs
 
LivezeyLab

Research

We work on cancers that express Estrogen Receptor α, including breast, ovarian, and uterine with a view to better understand and treat these cancers. We use a pre-clinical anti-cancer drug as a tool to probe the intricate pathways that allow cancer to grow, divide, and evade therapy.

 

The fundamental questions we are interested in addressing are the following:

1) How does the anticipatory unfolded protein response impinge upon cellular autophagy?

2) How can we utilize chemical and biological tools to study the interplay between these two pathways?

3) How is this complex interplay different than that between autophagy and the “classical” unfolded protein response?

 

The classical unfolded protein response is a cellular pathway that senses and responds to an excess of unfolded or mis-folded protein within the endoplasmic reticulum. Unfolded proteins cannot function properly and can become toxic, so the cell resolves this stress by turning on the protective unfolded protein response. We call our pathway “anticipatory” because it is activated in anticipation of a future increase in protein folding load, such as upon cell division.

Activation of the unfolded protein response has been shown to predict a worse prognosis in Estrogen Receptor α positive breast cancer patients. We work with a small molecule drug that hijacks this normally protective pathway, and elevates it to a level that is lethal within cancer cells. We are trying to better understand how this pre-clinical anti-cancer drug works, and how the anticipatory unfolded protein response is linked to other protective pathways within cancer cells.