New treatments for endocrine resistant breast cancer

Project Description: Estrogen receptor positive breast cancer is the most common breast cancer subtype, accounting for around two thirds of cases. Estrogen receptor positive tumours produce excessive amounts of a special protein, which drives the growth of these tumours. Professor Jonathan Baell from Monash Institute of Pharmaceutical Sciences (MIPS), has developed a set of preliminary drug candidates that can shut down expression of this important estrogen receptor positive breast cancer protein. This project aims to use drug design to optimize these inhibitors for improved anti-cancer killing and then test their effectiveness in breast cancer cells and patient derived breast cancer pre-clinical models.  

Why This Work is Needed: Although anti-estrogen therapy is effective for ER+ breast cancer tumours, around 30% of the tumours in these patients will develop resistance to treatment. The discovery of novel drug targets is essential to maintain high survival rate of breast cancer patients, especially those who do not respond or develop resistance to anti-estrogen therapy.  

Expected Outcomes: This study will investigate the potential of a special protein, a key enzyme involved in breast cancer cell growth as a drug target for the treatment of estrogen receptor positive breast cancer. The project will then produce a set of drugs that can block the action of this protein, and that may provide alternative treatment options for patients with estrogen receptor positive breast cancer who do not respond to standard of care treatments.  

Project Details  

Whilst initial treatment of estrogen receptor positive breast cancer using anti-estrogen therapy is effective, for around 3 in 10 patients with this type of cancer, drug resistance can develop within 5 to 10 years. Hence, alternative therapies for those who do not respond to this treatment are urgently required, either as a first-line treatment for those who do not respond to hormonal treatments, or as an option for those who have developed resistance to standard of care. 

Professor Jonathan Baell, from the Monash Institute of Pharmaceutical Sciences (MIPS), will lead this project to investigate new therapeutic options for estrogen receptor positive breast cancer. The team will optimise a set of drugs that target a novel key enzyme, involved in breast cancer growth, and which is overexpressed in estrogen receptor positive breast cancers. The research team has already established a set of preliminary candidate drugs and will further optimise each drug candidate in human breast cancer cells and in preclinical models of estrogen receptor positive breast cancer. 

Prof Baell expects that these drugs may result in a more long-term reduction in tumour growth and spread than current chemotherapy treatments. This would be a breakthrough for patients with estrogen receptor positive breast cancer that is resistant to anti-estrogen therapy.