Targeting proteins that help tumour cells to survive

Start Year: 2013
Finish Year: 2018
Chief Investigator: Professor Geoffrey Lindeman
Grant Type: Translational Grant
Institution: Walter and Eliza Hall Institute of Medical Research

Despite their capacity for relentless growth, breast cancer cells are poised in a life and death predicament. Pro-survival proteins such as BCL-2 family members are co-opted to resist cell death signals, thereby helping tumour cells to survive. BCL-2 is present in about 75% of breast cancers, where it is a recognised marker of prognosis . Its role in treatment hasn’t yet been determined.

Our recent work using mouse models has revealed that a new class of drug, the BH3 mimetic, is able to neutralise BCL-2 in primary breast tumours and thereby sensitise tumours to chemotherapy or anti-oestrogen therapy.

We will build on our earlier work and investigate how different BH3 mimetics work on their own and in combination with chemotherapy and anti-hormone therapy to treat breast cancer.

In parallel, we will also develop protocols for biomarkers, so we can incorporate these biomarkers into routine clinical practice and facilitate personalised therapy.

In partnership with the Translational Centre for Breast Cancer Research, we will conduct an early-phase clinical study of anti-BCL-2 therapy in ER positive and BCL-2-positive breast cancer. This will be the first clinical study of a BH3 mimetic in breast cancer. Our translational program will contribute laboratory and clinical data that will help pave the way for the development of this promising new class of drugs in breast cancer.