Prostate cancer (PCA) is the most common tumour affecting men, and represents a major healthcare burden worldwide. The androgen receptor (AR) is an important component, as it controls all stages of PCA to metastasis. It is activated by androgenic hormones, such as testosterone, and regulates gene expression. Dysfunctions can lead to several pathologies, including PCA. Current drugs targeting the AR stop being effective within five years, as new mutations alter the receptor’s structure and its response to treatment.
- To develop new precision medicines targeting the AR’s molecular behaviour (its dimerisation) to fight PCA, with a particular focus on the more aggressive and metastatic forms.
Problem to Solve
PCA is the second leading cause of cancer-related mortality in developed countries. While most patients face favourable outcomes, around 30% progress to more aggressive and highly metastatic forms of this tumour. In these cases, even if treatment options are initially effective, resistance to treatment will eventually occur within 3-5 years, leading to associated mortality.
The majority of efforts to fight PCA are aimed at developing drugs that compete with testosterone and derivatives to binding to the AR. However, this strategy is prone to drug-induced mutations that make the anti-androgens ineffective after a few years of treatment. The ARDIs strategy targets the AR’s dimerisation, a key aspect of its role as a gene regulator, which in turn can promote cancer progression.
Level of Innovation
The project has identified a new family of compounds with a new mode of action that inhibits AR dimerisation, opening the door to developing a new family of drugs to fight even the most aggressive forms of PCA.