Australian scientists have identified a potential mechanism to curb the spread of triple-negative breast cancer (TNBC), one of the most aggressive and deadliest forms of the disease. Researchers at the University of Adelaide and the Olivia Newton-John Cancer Research Institute have discovered a molecular pathway they believe could act as a 'brake' on metastasis, the process by which cancer spreads to other parts of the body.
TNBC accounts for approximately 10-15% of breast cancer diagnoses in Australia each year but is responsible for a disproportionate number of deaths. This is largely due to its aggressive nature and its tendency to resist many standard targeted therapies because it lacks specific hormone receptors and proteins. Treatment options for recurrent TNBC are particularly limited.
Understanding the Molecular Mechanism
The research team found that low levels of a naturally occurring molecule, miR-342, in cancer cells are associated with an overactive E2F system. The E2F system acts as an 'accelerator' for cell growth. When miR-342 is deficient, E2F can become overactive, potentially enabling cancer cells that have already spread to form new tumors in distant organs.
In pre-clinical tests, restoring miR-342 levels significantly reduced the spread of breast cancer to organs such as the lungs and bones. The study also indicated that palbociclib, an existing drug used for other advanced breast cancer types, could reduce the growth of metastatic tumors in models with low miR-342.
Implications for Treatment
Associate Professor Philip Gregory, co-senior author from the University of Adelaide's Centre for Cancer Biology and SA Pathology, highlighted that metastasis is the primary challenge in treating TNBC. "Most deaths from breast cancer occur because the cancer spreads to other parts of the body, rather than being caused by the primary tumor itself," Gregory stated.
Professor Robin Anderson, co-senior author from the Olivia Newton-John Cancer Research Institute, emphasized the importance of understanding metastasis, as it accounts for the majority of breast cancer fatalities. "Once cancer spreads throughout the body it becomes far more difficult to control," Anderson said.
The researchers suggest that assessing miR-342 levels in a patient's tumor could help identify a subgroup of women with TNBC who might benefit from palbociclib. This approach could lead to a more personalized treatment strategy. The study found that administering palbociclib after cancer cells had already spread was particularly effective in preventing microscopic metastatic tumors from growing into life-threatening secondary cancers.
The findings, published in EMBO Molecular Medicine, are currently based on laboratory and pre-clinical models. The researchers stress that further validation using patient-derived models is required before clinical trials in patients can commence. The study's authors noted that no statement in the article should be interpreted as medical advice, and all results cited pertain to pre-clinical studies.