Development of a new targeted treatment approach for triple negative breast cancers

Project Description: Triple negative breast cancer (TNBC) accounts for around 10-15% of breast cancer cases and is a highly heterogenous group of cancers, with limited targeted treatment options and poor overall survival outcomes. With the use of an innovative genetic screen, Prof Roger Daly and the team (Monash University) have identified a new potential druggable target (Citron Rho-interacting kinase (CIT)), that controls the growth of a subset of TNBCs. In parallel with a drug discovery program that will generate new targeted agents for CIT, Prof Daly and colleagues will investigate whether targeting CIT using genetic means can slow the growth of TNBCs in preclinical models. The investigators will then look for biomarkers that can identify those TNBCs dependent on CIT and therefore most likely to respond to anti-CIT therapy and finally identify drug response markers to assist with the development of new CIT targeting drugs.

Why the Work is Needed: Triple negative breast cancer is clinically challenging due to its aggressive nature and limited targeted therapeutic options. Patients with TNBC that develop metastatic disease have very poor survival outcomes. Hence, there is a desperate need to develop new and improved targeted therapies to improve the overall survival of TNBC patients.

Expected Outcomes: Successful outcomes of this study will validate the importance of the signalling molecule CIT as a druggable target for a subset of TNBCs providing the evidence needed to support the development of new drugs that can target this protein.

Project Details

Breast cancer is the second most common cancer among Australians and responsible for over 3,200 deaths every year. Despite significant improvements in the diagnosis and treatment of this disease, certain subtypes still present major clinical challenges. Triple negative breast cancer (TNBC) accounts for around 10-15% of breast cancer cases and is a highly heterogenous group of cancers, with limited targeted treatment options and poor overall survival outcomes.

Earlier proof-of-concept studies, using an innovative genetic screen conducted by Prof Roger Daly and the team, have identified a new target (Citron Rho-interacting kinase (CIT)), that controls the growth of a subset of TNBCs. This molecule is ‘druggable’, meaning small molecules can be developed to block its function and used therapeutically.

In this study, Prof Roger Daly (Monash University) aims to establish a precision oncology program designed to validate CIT as a potential new drug target for a subset of TNBCs. The therapeutic potential of targeting CIT alone or in combination with standard-of-care chemotherapy will be evaluated in preclinical models of TNBC where the CIT will be ‘turned off’, and the effect on tumour growth evaluated. Cutting-edge technologies will be used to identify predictive biomarkers able to identify patients most likely to benefit from anti-CIT therapy.  Finally, this study will identify potential drug response biomarkers to accurately measure the activity of the drug in cells and tissues. Outcomes from this study have the potential to successfully deliver a novel targeted approach for the treatment of a subset of TNBCs.