ARDIs First-in-class dimerisation inhibitors of the androgen receptor as a new treatment for prostate cancer

  • Edition: 2018
  • Research center: Fundació Bosch i Gimpera, Universitat de Barcelona
  • Scientific Area: Biochemistry and Molecular biology
  • Business area: Therapeutic
  • Status: In development
  • Contact: evaestebanez@ub.edu

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.

Goals

  • 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.

Innovation

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.

Team

Project leader

Eva Estébanez

Fundació Bosch i Gimpera / Universitat de Barcelona

Researcher

Pablo Fuentes

Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau

Postdoctoral researcher

Marta Nadal

Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau

Technician

Montse Abella

UB - Universitat de Barcelona

PhD student

Alba Jiménez

UB - Universitat de Barcelona

Head – Business Creation

José Conde

Fundació Bosch i Gimpera / Universitat de Barcelona

Mentor

CEO at Aelix Therapeutics

José Luis Cabero

Aelix Therapeutics & Symbiokraft

Partners

Obra social “la Caixa”
Caixa Capital Risc