Developing RNA-targeted therapy for metastatic triple-negative breast cancer

Project Description:

Despite significant advances in the early detection and treatment of breast cancer, cancer that spreads beyond the breast (known as metastatic disease) is incurable. Dr Behnam Rashidieh and colleagues have identified cancer-associated protein, CEP55, and shown that elevated levels of CEP55 correlate with cancer progression of several different cancers including triple-negative breast cancer (TNBC). This protein is a predictor of poor patient outcomes and promotes the progression of multiple cancers. In this NBCF-funded study, the team aims to use RNA-targeting therapeutics, similar to the approach of delivering COVID-19 vaccines, to target and block the action of CEP55 in TNBC metastatic laboratory experimental models.

Why is this work needed:

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer and often metastasises to the brain and lungs; with the highest mortality compared to other breast cancer subtypes. Hence, there is a need to develop new treatments to limit the progression or prevent metastatic breast cancer to reduce the deaths from this disease.

Expected outcomes:

Outcomes from this study have the potential to develop and evaluate an innovative therapeutic approach for hard-to-treat metastatic breast cancer.

Project description:

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with the lowest survival outcomes compared to other breast cancer subtypes which has a higher prevalence among younger women. TNBC accounts for up to 15% of all breast cancer cases and in Australia, this is around 3,000 new cases every year. TNBC is estimated to contribute to about 30% of all breast cancer-related deaths.

Dr Behnam Rashidieh and colleagues at the Mater Research Institute, University of Queensland have previously identified a protein (CEP55) as a cancer antigen and shown that elevated expression levels of CEP55 correlate with cancer progression of several different cancers including TNBC and is a predictor of poor patient outcome. Moreover, reducing the expression levels of CEP55 by inhibition of this protein in TNBC cells in a laboratory setting slowed their growth and the invasive nature of the cells.

With this NBCF support at the Mater Research Institute, University of Queensland, the team aims to use a novel therapeutic approach to target CEP55 and block the action of this protein in TNBC metastatic laboratory models. The team will develop and evaluate RNA-targeted therapeutics using clinically approved lipid nanoparticles to encapsulate and deliver synthetic DNAs to block CEP55 in cancer cells. This is a similar approach to that utilised in vaccines to deliver mRNA, for instance, against COVID-19.

This innovative therapeutic strategy could pave the way for new and innovative treatments for aggressive TNBC and metastatic cancer and improve outcomes for patients.