Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI) and Adelaide University have uncovered a promising new way to tackle one of the most aggressive forms of breast cancer, raising hopes for more effective treatments to stop the disease from spreading.
📸 (L-R): A/Prof Philip Gregory (Adelaide University), Prof Robin Anderson (ONJCRI)
The team found that triple-negative breast cancer (TNBC) patients with low levels of a naturally occurring molecule known as miR-342 and high activity of a cancer-driving pathway called E2F were more likely to develop metastatic disease, or secondary cancer.
TNBC is responsible for some of the poorest outcomes because it lacks the hormone receptors that make many other breast cancers treatable with existing therapies that target these receptors.
Co-senior author Associate Professor Philip Gregory, from Adelaide University’s Centre for Cancer Biology and SA Pathology, said metastasis (or cancer spread) remains the greatest challenge in treating TNBC.
“Our research identified a subgroup of patients whose tumours appear to rely on a specific molecular pathway to spread. By targeting that pathway, we were able to dramatically reduce metastatic growth in our laboratory models.”
A/Prof Gregory said the team discovered that miR-342 acts as a master regulator of an entire network of genes involved in cancer progression.
“When miR-342 levels fall, the E2F pathway becomes overactive, allowing dormant cancer cells that have already travelled through the body to grow into dangerous secondary tumours.”
Importantly, the existing breast cancer drug palbociclib, a CDK4/6 inhibitor currently used to treat advanced hormone receptor-positive breast cancer, significantly reduced the growth of metastatic tumours in models with low miR-342.
“Our findings suggest [these drugs] could also benefit a carefully selected group of patients with triple-negative disease.”
The researchers found that administering palbociclib after cancer cells had already spread was particularly effective in preventing microscopic metastatic tumours from growing.
Co-senior author Professor Robin Anderson from ONJCRI said:
“Rather than shrinking the primary tumour, this treatment may prove most valuable by stopping tiny metastatic deposits from developing into life-threatening secondary cancers.
“Our study identifies a distinct subgroup of patients whose cancers share a common biological weakness, opening the door to a much more personalised treatment approach.”
“TNBC is incredibly diverse, and that’s one of the reasons it has been so challenging to develop targeted treatments.”
The researchers say the next step is to validate the findings using patient-derived pre-clinical models before progressing to clinical trials.
TNBC accounts for around 10–15% of Australia’s approximately 21,000 breast cancer diagnoses each year but causes a disproportionate number of breast cancer deaths because of its aggressive nature and tendency to spread rapidly to distant organs.
The research team have dedicated this research paper to their collaborator, the late Dr Cameron Johnstone.
