Pioneering lower-dose combination treatments for breast cancer

Project Description:

Many breast cancers have changes in a protein called phosphoinositide 3-kinase (PI3K) that controls how cells grow. This change often leads to cancer cells not responding to standard treatment outcomes. While medicines that target PI3K have been developed, cancer cells can still find ways to resist these drugs. Associate Professor Lan Nguyen will investigate pathways that regulate how breast cancers develop resistance to PI3K targeting drugs and investigate new combinations of low dose drugs targeted to these pathways to treat PI3K-driven breast cancer. This low dose, multipronged approach could lead to better treatment outcomes and fewer side effects for many breast cancer patients, with the ultimate goal of reducing deaths while preserving the quality of life of breast cancer patients.

Why is this work needed:

Alterations in the PI3K protein is prevalent in different breast cancer subtypes, including 40% of estrogen receptor positive, 30% of HER2+ and 15% of triple negative breast cancers. These changes are linked to resistance to current treatments. Combination therapy shows promise, but conventional approaches often lead to unacceptable toxicity due to the high doses used and the overlapping toxic effects of individual drugs. Hence, there is the need to discover effective combinations of low-dose drugs with minimal adverse effects for PI3K-driven breast cancers.

Expected outcomes:

Successful outcomes of this study will reveal how breast cancer cells desensitise to PI3K-targeted drugs. Furthermore, a new method to identify combination treatments that target multiple cancer-driving proteins at lower doses but still effectively tackle PI3K-driven breast cancer will be developed. The combination of advanced biological experiments with computational modelling will generate results to improve therapy outcomes while reducing side effects.

Project description:

Over 20,000 Australians will be diagnosed with breast cancer in 2023, which equates to approximately 57 Australian each day. Furthermore, it is predicted that 9 Australians die in a single day from the disease. Resistance to treatment and subsequent development of metastatic breast cancer is the leading cause of breast cancer deaths. Treatment resistance can emerge either because tumours are inherently resistant or develop resistance over time. Alterations in a cellular signalling pathway led by a protein called phosphoinositide 3-kinase (PI3K), a key regulator of cell growth are highly prevalent in breast cancers. These changes in PI3K are associated with cancers resisting standard therapy.

With NBCF-support, Associate Professor Lan Nguyen at Monash University will use an innovative approach to address the challenges posed by breast cancers resistant to PI3K targeting drugs. This will involve combining cutting-edge biological experiments with advanced computational modelling to identify potential drug candidates and predict the most effective low-dose combination therapy for breast cancers with acquired changes in the PI3K protein. This combination low dose, multipronged approach could lead to better treatment outcomes with fewer side effects. The goal is to reduce deaths, all while minimising the impact on the quality of life of patients with breast cancer.