Targeting Wnt signalling to treat metastatic prostate cancer

Identifying potential new therapeutic biomarkers to improve patient care and increase survival rates.

About

Metastatic prostate cancer (mPC) is the primary cause of death in men with prostate cancer, owing to resistance to mainstay treatments such as androgen-deprivation therapy (ADT). Wnt signalling is frequently deregulated at the level of the Wnt ligand/Frizzled (FZD) receptor in mPC, including ADT-resistant disease, thus presenting a novel therapeutic target that is urgently needed in the clinic.

Aims

Our promising preliminary findings indicate that targeting Wnt signalling at the level of the Wnt ligand/receptor is efficacious against mPC in-vivo. Using several preclinical mPC models to recapitulate the clinic, this project will determine:

• the therapeutic benefit of WNT974 treatment (which blocks Wnt ligand secretion and is in Phase-I clinical trials for other cancers) in multiple disease subtypes (e.g.,+/-AR/Wnt pathway mutations)
• establish if FZD7 is the receptor transmitting Wnt signalling in mPC
• innovative in-vitro assays/RNAseq will also functionally/mechanistically examine how Wnt signalling regulates the activity of mPC cells when they encounter the primary metastatic site for PC, the bone

Findings will determine the efficacy of targeting the Wnt ligand/receptor against mPC, and will identify which PC cell genes are regulated by the bone during colonisation to identify potential new therapeutic targets/biomarkers, improving patient care and survival rates.

Funding

This project is funded by Prostate Cancer Research (PCR) charity through a project grant of £491,731 over 3 years.

People

Partners

• Dr Robert Jones and Professor John Staffurth from Cardiff University School of Medicine
• Dr Ning Wang from Sheffield University
• Dr Bin-Zhi Qian from The University of Edinburgh
• Dr Matt Smalley from Cardiff University School of BIOSI