Page 24 - Hormel Report 2021

Robert Clarke, Ph.D.
“Our research establishes mechanisms of drug resistance and identifies
new therapeutic targets for breast
cancer.”
Robert Clarke
24 | THE HORMEL INSTITUTE Cancer Systems Biology
EXECUTIVE DIRECTOR, THE HORMEL INSTITUTE / PROFESSOR
// UNIVERSITY OF MINNESOTA
More than 280,000 women are estimated to be newly diagnosed with breast cancer in 2021. Seventy percent of
these will express estrogen receptor alpha and can be treated with endocrine therapies- such as tamoxifen, aromatase inhibitors alone or in com- bination with CDK4/6 inhibitors. Unfortunately, more than 50% of these patients will develop resistance to endocrine therapies and do not have any targeted therapeutic option.
Our laboratory uses novel approaches to inves- tigate and understand the mechanisms respon- sible for endocrine therapy resistance in estrogen receptor positive breast cancer patients. We use multi-omics platforms
and mathematical and computational modeling to determine altered pathways responsible for endocrine therapy resis- tance. We further leverage that knowledge to discover novel targeted therapies and investigate its efficacy in vitro and in vivo models.
Current research projects
Cell communications in antiestrogen resistance:
This research project investigates the how endocrine therapy resistant cells communicate with the endocrine therapy sensitive and confer resistant phenotype to the sensitive cells in a heterogenous population. This project studies the how these dynamical changes are affected by gap junctions and microvesicle secretions. Other aims include building mathematical mod- els of cell population dynamical changes and learn the basic principles how resistant cells
affect responses in a mixed population. Also, we will analyze data sets from patients to find key features of molecular signaling associated with ER+ breast cancer recurrence.
Metabolic adaptations leading to endocrine therapy resistance: In this project we investigate the metabolic adaptations that are responsible for acquired/ de novo endocrine therapy resis- tance. We have identified high glucose uptake and glycolytic pathways that can be blocked by