Understanding the root of hormone therapy resistance
What you need to know
- Hormonal treatments, such as abiraterone and enzalutamide, are commonly used for advanced prostate cancer but eventually stop working as the cancer develops resistance.
- Dr Juan Manuel Jiménez Vacas hopes that by studying how the cells develop resistance, he may uncover new vulnerabilities in their defences which could be targeted.
- This may lead to new treatments that could be combined with existing drugs to keep the cancer under control for longer.
These drugs significantly improve how long patients live for, following the diagnosis of advanced prostate cancer. However, the medications eventually stop working, which is ultimately lethal. Therefore, we desperately need novel therapeutic approaches for these patients to improve not just their overall survival, but also their quality of life.
Dr Jiménez Vacas will study how prostate cancer cells become resistant to hormone therapies with the ultimate aim of identifying new ways to target them.
Blocking testosterone
Prostate cancer cells thrive on testosterone, so treatments such as abiraterone, enzalutamide and apalutamide work to reduce the levels of the hormone in the body or stop the cancer from benefiting from it. However, the cancer eventually becomes resistant and these treatments stop working. For men with advanced prostate cancer, this means that the disease is incurable.
Finding vulnerabilities
Previous research has found that prostate cancer cells change rapidly when they are treated with abiraterone. These changes may hold the key to discover how the cells become resistant, and may also uncover new vulnerabilities in the cancer that could be targeted with different drugs.
Dr Jiménez Vacas will use cells in the lab and samples from men with prostate cancer to do an in-depth study of how treatment resistance develops. This will help identify the key drivers of resistance and how they alter cells’ behaviour.
Targeting with existing drugs
As part of this fellowship, Dr Jiménez Vacas will spend six months working at Beth Israel Deaconess Medical Center at Harvard Medical School to analyse these changes in additional samples with different state-of-the-art technologies. Once he identifies key genes driving resistance, he will study their biological role and attempt to target them with drugs.
By the end of this project, Dr Jiménez Vacas expects to identify key molecular drivers of treatment resistance and uncover new targets for drug development. This approach could lead to the development of new drugs that could be used in combination with existing treatments like abiraterone or enzalutamide.
Grant information
Reference – TLD-PF19-006
Researcher – Dr Juan Manuel Jiménez Vacas
Institution – Institute of Cancer Research
Award - £268,435