Targeting PC4 with PROTACs to Eliminate Metastatic Triple-Negative Breast Cancer
Metastasis accounts for over 90% of cancer-related deaths, with triple-negative breast cancer (TNBC) among the most aggressive and metastatic subtypes. Current treatments often fail to eliminate metastatic cells. This project investigates Positive Cofactor 4 (PC4)—a transcriptional regulator overexpressed in TNBC and strongly associated with poor prognosis—as a novel therapeutic target. The team has developed a PC4-targeting PROTAC (Proteolysis Targeting Chimera) designed to degrade PC4, disrupt pro-metastatic signalling (notably TGF-β/SMAD2/3), and selectively kill metastatic cancer cells. This project aims to map PC4-driven pathways, optimise the PROTAC compound, and validate its safety and efficacy in advanced models. The work has potential to yield a first-in-class drug for TNBC and other PC4-driven cancers.