Research Project

Equimolar Co-administration of Synergistic CDK4/6 and MDM2 Inhibitors in Liposarcoma and Breast Cancer

Principal Investigator

Gauchat, Eric

Research Area(s)

Ongoing Projects

Abstract

A common driver of certain cancers is an upregulation of the proteins CDK4, CDK6, and MDM2. Together, these drive both increased cell growth and division while simultaneously preventing the cell’s natural apoptotic program from activating, even in cancers that have genetically intact p53. Studies in liposarcoma have shown that co-administration of CDK4/6 and MDM2 inhibitory drugs synergistically reduces cell growth and restores programmed cell death pathways. My research focuses on developing new classes of bifunctional molecules that ensure inhibition of both targets in every cell that takes up the drug, rather than the heterogeneous distribution observed with the coadministration of two drugs. We anticipate this will further amplify these positive effects while also reducing the prevalence of drug resistance, especially in inoperable tumors.