Towards more effective therapies for people with relapsed breast cancer

Project description

Estrogen Receptor Positive (ER+) breast cancer is the most common subtype of breast cancer (~70% of cases), accounting for the greatest number of relapses following initial treatment and breast cancer deaths. Although CDK4/6 inhibitors, the standard of care treatment for metastatic breast cancer, have dramatically improved people’s outcomes, relapse and treatment resistance may still occur.

Most relapsed ER+ breast cancers have higher levels of the BCL2 protein, a member of a family of survival proteins that allow cancer cells to evade cell death and stay alive. A type of targeted cancer therapy called BCL2 inhibitors is used to treat blood cancer, but little is known about the effectiveness of this emerging class of drugs in breast cancer.

Professor Geoff Lindeman and his team have taken the lead in transitioning BCL2 inhibitors to the clinic for people with relapsed breast cancer. In this NBCF-funded study, Professor Lindeman and his team from WEHI will build on insights from these trials and laboratory research. They will use laboratory models of human breast tumours to test more potent second-generation BCL2 inhibitors. This will include testing the BCL2 inhibitor on its own, in combination with a novel CDK4/6 inhibitor, and with other drugs involved in tumour growth and survival. Findings from this study aim to provide a deeper understanding of the role of survival proteins and to identify optimal strategies for targeting these proteins in relapsed ER+ breast cancer.

Why is this work needed

While significant progress has been made in the treatment of people with metastatic ER+ disease, relapse following treatment may still occur and subsequent treatment options are challenging. Given that ER+ breast cancer is the most prevalent subtype and is responsible for the highest number of breast cancer relapses and deaths, there is an urgent need for new treatment options.

Expected outcomes

The outcomes of these studies will deliver direct proof-of-concept data on novel drug combinations. Based on these results, the team aims to contribute to a clinical trial in people with advanced/metastatic ER+ breast cancer to evaluate safety, tolerability, the recommended dose, and treatment efficacy.