Evaluation of a Cdk9 inhibitor for the treatment of aggressive epithelioid hemangioendothelioma
Patients with aggressive epithelioid hemangioendothelioma (EHE), particularly those with metastatic disease, do not have effective treatment options. In this proposal, significant efforts have been devoted to identifying treatments that can reduce disease burden. If successful, these treatments can be repurposed for EHE treatment.
Previously, we identified a candidate protein, Cdk9, which is important for the stability of TAZ-CAMTA1 (TC), a fusion protein that causes EHE. Therefore, here, we rigorously evaluate available Cdk9 inhibitors, including those that were FDA-approved, and prioritize them based on their ability to destabilize TC. Aim 1.1 is a screen that will help prioritize Cdk9 inhibitors based on their ability to degrade TC. Aim 1.2 investigates whether Cdk9i prevents cancer cell growth and kills EHE cancer cells grown in plastic dishes. In Aim 1.3, we evaluate shortlisted treatments in mouse models of EHE. Our ultimate goal is to improve patient outcomes by repurposing a treatment that can reduce EHE metastasis.