In 2022, the EHE Foundation funded the Lamar Lab’s project entitled ‘Use of Pre-clinical EHE Models to Identify Druggable Pathways to Treat EHE,’ with the goal of identifying FDA-approved drugs that can be repurposed to treat EHE. By looking for drugs that are already FDA-approved, ideally, positive pre-clinical findings could be more rapidly translated to the clinic because the drug has been proven to be safe for use in people, overcoming a necessary but significant hurdle in new drug development. 

Using EHE cell lines generated from the Rubin Lab engineered mouse model, the Lamar lab conducted a drug screen and discovered 17 drugs capable of blocking EHE cell growth and survival. The screen prioritized drugs with fewer potential side effects, focusing on those that target EHE cells without harming normal cells. Of the 17 drug candidates, 5 met this criterion, and remarkably, 4 were statins, a safe and widely used class of drugs prescribed to lower cholesterol and reduce cardiovascular risk.

The lab found that Statins dramatically reduce both the proliferation (growth) and survival of EHE cells, not by lowering cholesterol, but by inhibiting an enzyme required to activate Ras-GTPases, a family of proteins that drive cell growth and survival. These results were independently confirmed in a human EHE cell line, strengthening the lab’s findings. 

The lab is currently testing whether Statins can suppress the growth of aggressive human EHE tumors in mice (in vivo). Since Statins are considered safe for long-term use, the lab is also exploring their potential to control or manage indolent EHE, similar to managing a chronic disease. 

While data so far is not yet sufficient to warrant the use of Statins in patients, if the ongoing work is successful, it will provide the preclinical data needed to support the initiation of a clinical trial in EHE patients. This body of work could transform a familiar, well-tolerated drug into a new targeted therapy for EHE.