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 and breast cancer deaths. Although CDK4/6 inhibitors have dramatically improved outcomes for patients with relapsed ER+ breast cancer, resistance to therapy is common. Most relapsed ER+ breast cancers have elevated levels of BCL2, a member of a family of pro-survival proteins that allow cancer cells to evade death. The BCL2 inhibitor (venetoclax), a targeted cancer therapy, is in use for the treatment of blood cancer but beyond blood cancers, little is known about the effectiveness of this emerging class of drugs.

Professor Geoff Lindeman and colleagues have taken the lead in the efforts to transition BCL2 inhibitors to the clinic for patients with relapsed breast cancer including several clinical trials. Building on insights from these trials and laboratory research, in this NBCF-funded study Professor Lindeman and the team from The Walter and Eliza Hall Institute of Medical Research will use laboratory models of human breast tumours to evaluate more potent second generation BCL2 inhibitors. This evaluation will include testing the inhibitor alone, 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 BCL2 pro-survival family of 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 patients with metastatic ER+ disease, relapse is common 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 this 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 patients with advanced/metastatic ER+ breast cancer to evaluate safety, tolerability, the recommended dose, and treatment efficacy.