Uncovering new indicators and treatments for triple-negative breast cancer metastasis

Project Description:

Triple Negative Breast Cancer (TNBC) accounts for around 10-15% of all breast cancer cases – around 3000 new cases of TNBC every year – and can be difficult to treat. Compared to other breast cancers, TNBC spreads frequently to other organs (known as metastasis), resulting in poor survival outcomes. Associate Professor Philip Gregory and colleagues have previously found that high levels of a molecule known as ZCCHC24 are linked to poor outcomes in people with TNBC. In this NBCF-funded study, the team will examine the role of ZCCHC24 in the metastatic progression of TNBC in laboratory experimental models, and explore the mechanism by which ZCCHC24 reprograms TNBC cells to spread, potentially yielding insights into the use of this molecule as a diagnostic and predictive indicator of the likelihood of breast cancer to metastasis, and improved treatment options for TNBCs.

Why is this work needed:

TNBC can be difficult to treat, and it can commonly spread to other part of the body such as the lungs and bone, leading to what is known as metastatic disease. Current therapies for TNBC include chemotherapies, which can have toxic side effects, and immune therapies may only benefit some people with TNBC. As survival rates for metastatic TNBC remain low, there is a need to gain a better understanding of the aggressive features of TNBC cells to develop new and targeted therapies to prevent the spread of the cancer and improve survival outcomes.

Expected outcomes:

Successful outcomes of this study will reveal whether a molecule, ZCCHC24, can be used as a diagnostic and predictive marker of TNBC becoming metastatic. This could provide valuable insights for improved treatment options for people diagnosed with TNBC.

Project description:

TNBC is an aggressive form of cancer which can spread beyond the breast (known as metastasis) and return after treatment. It also has a higher prevalence among younger women. TNBC accounts for around 10- 15% of all breast cancer cases and in Australia, this is around 3000 new cases of TNBC every year. TNBC is estimated to contribute to about 30% of all breast cancer-related deaths. This can be attributed in part to the lack of effective treatment options. Current therapies mainly involve chemotherapy, which can have toxic side effects, and immunotherapies that only benefit a small number of people.

The ability of cancer cells to change and help them spread to other parts of the body, known as cancer cell plasticity, contributes to making TNBC harder to treat. Understanding the molecular events that drive cancer cell plasticity could lead to new treatment options to limit or prevent cancer progression.

Prior research led by Associate Professor Philip Gregory at the University of South Australia identified a protein (ZCCHC24) and showed that high levels of this protein cause TNBC cells to become more invasive.

With NBCF support, the team aims to examine a large cohort of samples from people diagnosed with TNBC to determine if levels of ZCCHC24 in cancer cells can serve as a diagnostic and predictive indicator of the likelihood of breast cancer to become metastatic. Moreover, the team will investigate the molecular mechanism by which ZCCHC24 drives the development of metastatic cancer.