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An existing breast cancer drug may have a new role in treating one of the most aggressive forms of the disease after researchers identified a molecular pathway that appears to drive the spread of triple-negative breast cancer.
Researchers from Adelaide University and the Olivia Newton-John Cancer Research Institute found that low levels of a naturally occurring molecule called miR-342, combined with high activity in a cancer-driving pathway known as E2F, were associated with a greater likelihood of metastatic disease.
In preclinical models, restoring miR-342 markedly reduced the spread of breast cancer to other organs, including the lungs and bones. Researchers also found that palbociclib, a CDK4/6 inhibitor currently used to treat advanced hormone receptor-positive breast cancer, significantly reduced the growth of metastatic tumors in models with low miR-342.
The findings, published in EMBO Molecular Medicine, suggest that measuring miR-342 levels could potentially help identify a subset of patients with triple-negative breast cancer, or TNBC, who may benefit from CDK4/6 inhibitors.
The research remains preclinical. The researchers say they must validate the findings using patient-derived preclinical models before progressing to clinical trials.
Why Triple-Negative Breast Cancer Is So Difficult to Treat
Triple-negative breast cancer lacks the hormone receptors and HER2 proteins targeted by many existing breast cancer therapies, leaving fewer targeted treatment options.
“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,” said co-senior author Associate Professor Philip Gregory, of Adelaide University’s Center for Cancer Biology and SA Pathology.
“Triple-negative breast cancer is particularly difficult to treat because it lacks the hormone receptors and HER2 proteins upon which many targeted therapies rely. While immunotherapy is improving outcomes for some patients, treatment options remain very limited once the cancer returns.
“Our research identified a subgroup of patients whose tumors 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.”
TNBC accounts for approximately 10% to 15% of Australia’s roughly 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.
Researchers Identify a Molecular Switch Behind Metastasis
The researchers found that miR-342 regulates a network of genes involved in cancer progression.
“When miR-342 levels fall, the E2F pathway becomes overactive, allowing dormant cancer cells that have already traveled through the body to grow into dangerous secondary tumors,” Gregory said.
The discovery is particularly notable because drugs that target this pathway already exist.
“The exciting aspect of this discovery is that drugs targeting this pathway already exist. CDK4/6 inhibitors are routinely used for patients with advanced hormone receptor-positive breast cancer, and our findings suggest they could also benefit a carefully selected group of patients with triple-negative disease.”
The findings do not suggest that CDK4/6 inhibitors would work for all patients with TNBC. Instead, the research points to a potentially identifiable subgroup whose tumors share a particular molecular vulnerability.
Palbociclib Targets Metastatic Growth in Preclinical Models
Researchers found that administering palbociclib after cancer cells had already spread was particularly effective at preventing microscopic metastatic tumors from growing.
Co-senior author Professor Robin Anderson, of the Olivia Newton-John Cancer Research Institute, said understanding what drives cancer beyond the primary tumor is critical because metastatic disease is responsible for most breast cancer deaths.
“Primary tumors can often be treated successfully with surgery or local therapies, but once cancer spreads throughout the body it becomes far more difficult to control,” Anderson said.
“Triple-negative breast cancer is incredibly diverse, and that’s one of the reasons it has been so challenging to develop targeted treatments.”
The potential significance of palbociclib in the study was not primarily its effect on the original tumor, but its ability to interfere with metastatic growth.
“Rather than shrinking the primary tumor, 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 personalized treatment approach.”
What This Could Mean for Nurses
For oncology nurses, the research underscores how tumor biology and biomarkers are increasingly shaping cancer treatment decisions.
If clinical trials validate the findings, measuring miR-342 could help identify a subset of patients with TNBC who may benefit from a more personalized treatment strategy. The research could also expand the potential use of a drug class already used to treat some patients with hormone receptor-positive breast cancer.
The study does not establish palbociclib as a treatment for triple-negative breast cancer. The researchers demonstrated its effects in preclinical models, and additional research is needed to determine whether the approach is safe and effective in patients.
The researchers’ next step is to validate the findings in patient-derived preclinical models before progressing to clinical trials.
